Transcript Jan Zolkower, MSHL, CIP, CCRP May 3, 2013

Writing an IRB
Protocol
Jan Zolkower, MSHL, CIP, CCRP
May 3, 2013
Financial Disclosure
The speaker does not have a financial
interest or relationship.
Agenda
 Why a protocol is necessary
 What components need to be included in
the protocol
 Examples of protocol sections
Why is this
important
information?
OHRP Determination Letter
 Ellen Roche, a healthy volunteer, died as
a result of her participation in a research
study at John Hopkins.
 OHRP noted “the investigators and the
IRB failed to obtain published literature
about the known association between
hexamethonium and lung toxicity.”
Writing an IRB Protocol
Critical Points
 All research protocols expose
participants to some degree of risk.
 The written protocol should support the
results of a trial.
 If the protocol is poorly written, no
subsequent analysis may be able to
salvage the trial.
Why is a Protocol Important to
the IRB
 The VU IRB requires a protocol for
consistency in the review of research.
 A protocol serves as the reference point
for review of a Health
Science/Biomedical IRB Application.
Challenges
 Write a protocol to address all scenarios.
 Create an effective road map to guide
anyone who may become involved with
the trial.
 To stay within the parameters of the
protocol (do only what you say you are
going to do…not more or less).
 Make sure the study is scientifically
sound and has statistical power.
Creating an IRB Protocol
 Identify the question the study will
answer.
 Conduct a literature search.
 Identify any investigational
agents/devices.
Title Page
 State the full protocol title.
 Provide the PI’s name and address.
 State who will be supporting the study.
 State the date of the protocol.
 Optional: Names of Sub-PI’s
IND or IDE holder
Sample Title Page
Protocol Title
The Effects of Tagalong Peanut Butter
Girl Scout Cookies:
A Randomized Trial
Principal Investigator’s name and address
James Jones, M.D., Department of Medicine
Vanderbilt University, 504 Oxford House, 4315
Sub-Investigators and their affiliations
Jane Doe, M.D., Department of Medicine,
Vanderbilt University
Version Date
April 23, 2013
Table of Contents
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Study Schema
1.0 Background
2.0 Rationale and Specific Aims
3.0 Animal Studies and Previous Human Studies
4.0 Inclusion/Exclusion Criteria
5.0 Enrollment/Randomization
6.0 Study Procedures
7.0 Risks of Investigational Agents/Devices (side effects)
8.0 Reporting of Adverse Events or Unanticipated Problems involving Risk
to Participants or Others
9.0 Study Withdrawal/Discontinuation
10.0 Statistical Considerations
11.0 Privacy/Confidentiality Issues
12.0 Follow-up and Record Retention
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Appendices
1.0 Background
 Provide the history of the topic and why
the research is important. Include any
pertinent pre-clinical, pilot, and
preliminary and/or unpublished data to
support the conduct of the proposed
study.
 Include information about the disease,
the number of people it affects, and how
it affects the population.
Background
 Over the past 8 decades, the number of boxes of
cookies being sold by girl scouts has steadily
increased. Although studies have been conducted
by the Girl Scouts of America regarding what may
motivate young girls to lead a healthier lifestyle
(Schoenberg, 2006), research has not been
conducted on the potential benefits or risks
associated with the consumption of the cookies to
determine its impact on the health of the
American population. This study will examine how
consuming the Tagalong peanut butter cookie
affects glucose and cholesterol levels.
2.0 Rationale and Specific
Aims
 State the hypothesis and scientific justification
for conducting the study or why something
which is widely accepted needs to be
challenged (new information or findings).
 Be sure to justify the target population,
endpoints, and why particular techniques will be
used for endpoint assessment, measurement of
drugs, drug effects, etc.
 Clearly differentiate the specific aims in order of
importance.
Rationale and Specific Aims
 Each year, thousands of boxes of girl scout
cookies are sold and consumed. However, the
ramifications of subjecting the human body to
sudden increases in sugar and fat has yet to be
explored. The effect on heart disease,
hyperglycemia, and weight gain needs to be
examined to determine if warnings labels need
to be added to the product packaging and to
determine how long it will take for serum and
cholesterol levels to return to baseline.
 Include information on diabetes, heart
disease, etc.
Rationale and Specific Aims
 The specific aims will be:
1) To characterize the relationship between
consumption of girl scout cookies and health risks;
2) To monitor changes in glucose and cholesterol
levels after consuming the study agents for a period
of up to 30 days; and
3) To determine how long it will take for glucose and
cholesterol levels to return to baseline.
3.0 Animal Studies and
Previous Human Studies
 Note other human or animal research on
the topic and provide any references that
are relevant to the design and conduct of
the study.
4.0 Inclusion/Exclusion
Criteria
 List the criteria:
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Bullet or number each criteria for easy
identification
Explain the procedures to determine
eligibility
Note any special assessments that will be
conducted (e.g., depression or suicidal
ideation screenings)
Inclusion/Exclusion Criteria
 Inclusion Criteria:
Healthy volunteers
Between the ages of 18-80
 Exclusion Criteria:
History of heart disease, uncontrolled diabetes
Allergic reaction to peanuts or chocolate
Inability or unwillingness to give informed
consent
5.0 Enrollment/Randomization
 State how participants will be identified and
recruited for the trial.
 Describe the procedure for consenting
participants.
 Do potential participants have a relationship
with the PI? If so, how will the PI remain
impartial when presenting the study?
 How many participants will be consented and
how many are anticipated to complete the trial?
5.0 Enrollment/Randomization
 Will any vulnerable populations be
enrolled?
 How long will the study last?
 Does the study include blinding?
 Will participants receive a placebo?
 State the ratio for randomization (1:12:1).
 Will the PI provide the pharmacy with a
randomization schedule?
Enrollment/Randomization
 Participants will be selected from the…
 After expressing interest in the study, the
coordinator will provide an overview of
the study and obtain consent prior to
initiating any research related
procedures.
 Approximately xx participants will be
consented with xx being expected to
complete the study.
Enrollment/Randomization
(cont)
 Participants will be randomized to
receive either the active study agent or
the placebo (1:1 ratio).
 Study agents will be provided by Girl
Scouts of America and will be stored and
dispensed through the Investigational
Drug Service.
6.0 Study Procedures
 Will patients be withdrawn from current
medications or other treatments?
 Is there a run-in period?
 Will participants have a baseline
assessment for the status of the disease
being studied?
 Are overnight stays involved?
 Who will administer the study drug?
6.0 Study Procedures
 Discuss doses and length of exposure to
study drugs.
 Outline what will occur at each visit
(labs, assessments, other tests).
Consider including a chart or table.
 State measures that will be used to
minimize risk and monitor participant
safety.
Study Procedures
 Participants will be asked to come to the clinic, and
upon arrival will have their blood drawn (10ml).
Once the blood draw is complete the participant will
be asked to consume the study agent. After a 30
minute rest period, a second blood draw (10ml) will
be performed. The participant will be asked to
consume a second study agent and will return to
the waiting area. After another 25 minute rest
period the participant will be asked to consume the
final study agent and the blood draw (10ml) will be
repeated. Patients will be monitored for signs or
symptoms of an allergic reaction for an additional 60
minutes after the blood draw prior to being released.
Study Procedures
 Subjects will be discharged with a 30
day supply of the study agent and will be
asked to consume 6 study agents per
day.
 Weekly phone calls will be made to
monitor for adherence and safety.
 A follow-up visit with a blood draw (10ml)
will be conducted at the clinic between
days 28-32. Participants will return any
unused study agents at that time.
Study Procedures
 Three additional follow-up visits will be
conducted at approximately 60, 90, and
120 days. Participants will be asked to
provide a blood sample (10ml) at each
visit to monitor glucose and cholesterol
levels.
Study Procedures
 Participants will not be withdrawn from
any current meds. The study agents will
be administered by the study staff while
at the study center and self-administered
at home.
 Participants will be monitored for safety
and compliance through weekly phone
calls, which will be made by the study
staff and will follow an approved script.
7.0 Risks
 State all adverse events observed in
other previous animal or human studies
or any laboratory observations.
 Note if there may be unknown risks
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Because this treatment is investigational,
meaning non-FDA approved, there may be
risks that we do not know about at this
time.
Risks
 The active study agent contains peanut
products. The risks associated with
peanut allergies can range from a mild
rash to an anaphylactic reaction.
 Other side effects:
Weight gain
Blood draw risks
Rank according to common, uncommon
and life-threatening/severe.
8.0 Reporting of Adverse Events
or Unanticipated Problems
 What will be reported – be clear and
specific.
 State the Data Safety Monitoring Plan.
 Is there a Data Safety Monitoring Board?
If so, who are the members and how
often will they meet?
 Provide reporting procedures to the
sponsor, IRB, or federal agencies.
Reporting Adverse Events
 All anaphylactic reactions will be
promptly reported to the IRB.
 The PI will be responsible for monitoring
each participant during the study and for
60 minutes after the final ingestion of the
study agent. Participants will be
contacted on a weekly basis while
receiving the study agents to monitor for
adherence and adverse events.
9.0 Study
Withdrawal/Discontinuation
 Explain the procedures for withdrawing a
participant who decides to stop the study
and the circumstances under which the
PI would withdraw the participant
(unacceptable adverse events, noncompliant, etc).
Study Withdrawal/Discontinuation
 Participants may withdraw from the
study at any time. The study agent
should not be stopped abruptly, but
should be tapered instead.
 The PI will withdraw any participant who
experiences an unacceptable adverse
event or is non-compliant.
10.0 Statistical Considerations
 Provide evidence the study has adequate power to
detect a difference between the two groups or to
answer the question being asked.
 If the study could have multiple outcomes, has a
power analysis been conducted for each outcome?
 Will an interim analysis be conducted to determine
any difference between the study groups?
 Will predetermined rules be established for stopping
the study due to futility?
Statistical Considerations
 Please consider using REDCap.
 Features include:
 Scheduling
 Building surveys
 Exporting data to Microsoft Excel, PDF, SIS,
Stata, R, or SPSS for analysis
 Advanced features: auto-validation,
calculated fields, file uploading,
branching/skip logic and survey stop actions.
Statistical Consideration
 The primary endpoint is change from the
baseline of blood glucose and
cholesterol levels at 30, 60, 90 and 120
days.
11.0 Privacy/Confidentiality
Issues
 How will the privacy and confidentiality of
participants be protected?
 Will data be coded, stored in a password
protected computer?
 Who has access to the code?
 Is information being shared with other
Investigators or institutions?
Privacy/Confidentiality
 All study related materials will be
maintained in a locked file cabinet or
stored in a password protected,
encrypted electronic database. Only the
PI and study coordinator will have
access to the cabinet key or password.
Information will not be shared with other
investigators or institutions.
12.0 Follow-up and Record
Retention
 How long will patients be monitored or
possibly screened for signs of disease?
 If there is evidence of disease, what
procedures will be followed?
 How long will records be maintained
after study completion? (Must be a
minimum of 3 years)
Followup/Record Retention
 Participants will receive weekly follow-up phone
calls and will return to the clinic for 4 follow-up
visits. At each contact, participants will be
asked if they have experience any adverse
events.
 All study related documents will be retained by
the Investigator for a minimum of 6 years. At
this time, all records will be destroyed in
accordance with HIPAA and institutional
policies and procedures.
Miscellaneous Sections
 Blinding/Un-blinding Procedures
 References
Why is this
important to the
IRB?
Criteria for IRB Approval
(45 CFR 46)
 Risks to subjects are minimized
 Risks are reasonable in relation to anticipated
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benefits
Selection of subjects is equitable
Informed consent is obtained when required
Informed consent is appropriately documented
Data and safety monitoring is adequate
Privacy and confidentiality are protected
Additional safeguards are in place for
vulnerable populations
Reviewer Comment Form
Reviewer Comment Form
References
 OHRP Determination Letter to John Hopkins is located
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at: http://www.hhs.gov/ohrp/detrm_letrs/jul01a.pdf
Schoenberg, 2006. The New Normal? What Girls Say
About Healthy Living.
http://www.girlscouts.org/research/publications/original/he
althy_living.asp
IRB Policy VI.B, General Responsibilities of the
Investigator
FDA (Investigational Drugs)
http://www.fda.gov/cder/info/healthcare.htm
FDA (Investigational Devices)
http://www.fda.gov/cdrh/
QUESTIONS?
 Contact information for future questions:
[email protected]
(615) 343-8395
THANK YOU!!