Transcript The Fundamentals of Clinical Research

1
The Fundamentals of Clinical Research
Prepared by Christine Hunter, BSN
Baylor College of Medicine
and
Karen Williams, CCRP
Northwestern University
2
What is research?
Research is defined by the Department of Health and
Human Services as a systematic investigation,
including research, development, testing, and
evaluation designed to develop or contribute to
generalizable knowledge.
Systematic
45 CRF 46 Common
Rule
• Defined procedure for data collection process
• Primary and secondary endpoints are defined prior to data analysis
• Data is gathered and then analyzed
Generalizable
• Hypothesis is tested
• Research outcomes are shared
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Types of Research
Interventional
observational
• A study that uses an
intervention to modify the
health of the subjects
• Administration of a drug or
device; medical procedure
• Manipulation of the
environment intended to
change the course of a
subject’s medical condition
• A study without clinical
intervention (i.e. survey or
questionnaire)
• An evaluation of patient
condition (i.e. PPMI)
• An assessment of data
collected on an individual or
group of patients (i.e. PPMI)
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Clinical Trials
Sponsor
Funder
• The person, company, or
group who wrote the protocol
and takes responsibility for the
initiation, management,
reporting, and document
preparation of the trial, as per
FDA requirements.
• Source of funding to support
the conduct of the trial;
funding may come from the
sponsor or another source.
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Clinical Trials
Industry Sponsored
Investigator Sponsored
Grant Funded Clinical
Protocols for a clinical
investigation that are
written and initiated by a
person or agency outside of
the institution
Protocols for a clinical
A clinical investigation that
investigation are initiated
is funded by the NIH or
and conducted by the same other granting agencies
person, usually a faculty
member
The person or agency does
not actually conduct the
investigation, but pays
clinical investigators for
their participation
Investigator initiated trials
carry the same regulatory
requirements as industry
sponsored trials, so the
investigator takes on ALL
sponsor responsibilities
Subject to further
restrictions and
requirements that are
placed on all federally
funded project
The external sponsor takes
responsibility for the
initiation, management,
reporting, and document
preparation of the trial
Funding sources could be
externally funded, grant
funded, or unfunded
The NIH uses activity
codes (e.g. R01, R43, etc.)
to differentiate the wide
variety of research-related
programs they support
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Human Subjects
A human subject is a living individual about whom
an investigator obtains data through
intervention or interaction or identifiable private
45 CRF 46.102
information.
HIPAA regulations cover research on all human
subjects, living or deceased
Identifiable specimens or records of deceased
subjects may require approval by the IRB
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Primary Investigator
• An individual who actually conducts a clinical
investigation, i.e. under whose immediate
direction the test article is administered
Eligible to serve as the PI
Case-by-Case Determination
•Curators
•Instructors
•Librarians
•Non-tenure-track research and
clinical faculty
•Tenure-track faculty
•Senior research investigators
•Adjunct faculty
•Visiting faculty
•Visiting scholars
NOT Eligible to serve as the PI
•Postdoctoral fellows
• Research assistants
•Graduate students
•Research associates
Contact the Associate Vice President •Undergraduate students
for Research via email to request
permission for such faculty. Please
include your CV.
If approval is granted, upload the
confirmation email as a supporting
document into the eIRB+
application.
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PI Responsibilities
21 CRF 312.60
An investigator is responsible for
ensuring that an investigation is
conducted according to the signed
investigator statement, the
investigational plan, and applicable
regulations; for protecting the
rights, safety, and welfare of
subjects under the investigator's
care; and for the control of drugs
under investigation. An investigator
shall, in accordance with the
provisions of part 50 of this chapter,
obtain the informed consent of each
human subject to whom the drug is
administered, except as provided in
50.23 or 50.24 of this chapter.
21 CRF 812.100
An investigator is responsible for
ensuring that an investigation is
conducted according to the signed
agreement, the investigational plan
and applicable FDA regulations, for
protecting the rights, safety, and
welfare of subjects under the
investigator's care, and for the
control of devices under
investigation. An investigator also is
responsible for ensuring that
informed consent is obtained in
accordance with part 50 of this
chapter. Additional responsibilities
of investigators are described in
subpart G.
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Components of a Budget
• Start-up fees
▫ Pharmacy
 $300 Federally funded and investigator initiated
studies
 $3000 Sponsored studied
▫ IRB, sponsored research only
• Clinical Care Expenses
• Study Team Effort
• Indirect Costs
▫ Non-federally funded
▫ Federally funded
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Pharmacy Fees
STUDY DOSING INDUSTRY
FEES
SPONSORED
NON-INDUSTRY
SPONSORED*
Prescription
$50 /
prescription
$15 / prescription
IV
$100 / dose –
low
$250 / dose high
$45 / prescription
OPERATING
FEES
INDUSTRY
SPONSORED
NON-INDUSTRY
SPONSORED*
Initiation
$3,000
$300
High
Medium
Low
$1,000
$700
$300
$50
Drug
Compounding
$60/hour
$30/hour
Annual
Maintenance
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FACILITIES AND ADMINISTRATIVE RATES
Federally Funded
NATURE OF
SPONSORED
ACTIVITY
ON/OFF CAMPUS
Sponsored Research
On Campus
Off Campus
Non-Federally Funded
FY 2015
09/01/14 - 08/31/15
54.5%
26.0%
FY 2016
09/01/15 - 08/31/16
AND THEREAFTER
(PROVISIONAL)
54.5%
26.0%
Department of
Defense (DoD)
Contracts
On Campus
Off Campus
55.5%
26.0%
55.5%
26.0%
Sponsored
Instruction/Training
On Campus
Off Campus
51.0%
26.0%
51.0%
26.0%
Other Sponsored
Activity
On Campus
Off Campus
36.0%
26.0%
36.0%
26.0%
ON/OFF CAMPUS
On Campus
Off Campus
FY 2015
09/01/14 08/31/15
64.4%
31.3%
FY 2016
09/01/15 08/31/16 AND
THEREAFTER
(PROVISIONAL)
64.4%
31.3%
Sponsored
Instruction/Training
On Campus
Off Campus
78.3%
51.9%
78.3%
51.9%
Other Sponsored
Activity
On Campus
Off Campus
42.8%
31.8%
42.8%
31.8%
IndustrySponsored Clinical
Trials
On Campus
Off Campus
30.0% (TDC)
30.0% (TDC)
30.0% (TDC)
30.0% (TDC)
NATURE OF
SPONSORED
ACTIVITY
Sponsored
Research
**Check institutional rates as these vary by institution
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Clinical Trials:
From Concept to Implementation
Drug
Development
Pre-Clinical Drug
Discovery
Investigational
New Drug
IND submitted to
FDA for use of
therapy in human
clinical trials
Clinical
Research
New Drug
Application
Animal Research
Phase I
Phase II
Phase III
• Small Cohorts
• Healthy Volunteers
• Dose Escalation
• Toxicity
• Disease Specific
• Drug vs. Placebo
• Safety
• Large Cohorts
• Drug vs. SOC
• Efficacy
Approval for
marketing based
on clinical trial
results
Phase IV
Post-Marketing
Monitoring
In Vitro Tests
• Long Term Safety data
• Diverse Populations
• Observational
• Registries
Ongoing Drug
Safety Monitoring
MEDWatch
reporting by
consumers and
physicians
In Vivo Tests
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Pre-Clinical Drug Discovery
• Compounds are extracted from natural
substances or synthesized in the lab and
analyzed for therapeutic value
• Pre-clinical testing:
▫ Pharmacology
 Pharmacodynamics
 Pharmacokinetics
▫ Toxicology
▫ Animal testing
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Pre-Clinical Testing
Pharmacodynamics
• The observed effect resulting from a certain drug
concentration
Pharmacokinetics
• Describes the drug concentration-time courses in body fluids
resulting from administration of a certain drug dose
▫
▫
▫
▫
Absorption
Distribution
Metabolism
Excretion
Toxicology
• Tests the toxicological effects of an agent, including
carcinogenicity
Animal Studies
• Common animal models for studying compound safety and
efficacy include mice, rats, pigs, dogs, and monkeys
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Research & Development Statistics
• The average cost of R&D for every successful
drug is $800,000,000-$1,000,000,000
• For every 5,000-10,000 compounds in the R&D
pipeline, 1 receives FDA approval
• The Pharmaceutical Research Manufacturers of
America (PhRMA) estimates that only 5 in 5,000
compounds that enter pre-clinical testing make
it to human testing, and 1 of those 5 might be
safe and effective enough to reach pharmacy
shelves
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Pre-Clinical Testing Results
• When a drug has undergone sufficient
laboratory and animal testing, the sponsor must
submit an application to the FDA prior to testing
the new drug in humans
• The FDA will review the pre-clinical data and the
proposal for human clinical trials design
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Essential Elements of a Protocol
•Objectives should be
clearly stated as
hypotheses to be tested
•Inclusion and Exclusion
criteria should be
explicitly stated
•Sufficient background
information should be
included so that the
rationale for the study is
clear
Objectives
Background
Patient
Eligibility
Criteria
Pharmaceutical
Information
•Information should
include product
description, storage
requirements, stability,
route of administration,
and toxicity information
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Managing Bias
Controlled
Trials
Study Drug vs. Placebo
Randomization
Blinding
Subjects are randomly
assigned to a specific arm
of the study
Single Blinding: the
patients do not know
whether they are
receiving study drug or
placebo
The investigator does not
control randomization
Double Blinding: the
patients, investigators,
study staff, and data
analysts do not know
whether they are
receiving study drug or
placebo
Similar Age and Weight
Same Stage of Disease
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Blinding
The FDA considers blinded clinical trials ethical if
they meet the following criteria:
• Patients are fully informed of the protocol and
treatment options
• Treatments cannot be denied that could prevent
irreversible injury or alter survival
• Continuous monitoring looks for negative or
positive results
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Clinical Trial Blinding
• Human behavior is influenced by what we know or believe. In research
there is a particular risk of expectation influencing findings, most obviously
when there is some subjectivity in assessment, leading to biased results.
Blinding (sometimes called masking) is used to try to eliminate such bias.
• Double blind, usually refers to keeping study participants, those involved
with their management, and those collecting and analyzing clinical data
unaware of the assigned treatment, so that they should not be influenced by
that knowledge.
• Double-Dummy, two active compounds, blinding is possible using the
this method. For example, if we want to compare two medicines, one
presented as green tablets and one as pink capsules, we could also supply
green placebo tablets and pink placebo capsules so that both groups of
patients would take one green tablet and one pink capsule.
• Single blind trials (where either only the investigator or only the patient is
blind to the allocation) are sometimes unavoidable.
• Open (non-blind) trials. In trials of different styles of patient
management, surgical procedures, or alternative therapies, full blinding is
often impossible.
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Investigational New Drug (IND)
IND Submission contents
When to submit an IND
•
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•
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Introductory statement
Investigational plan
Investigator’s brochure
Protocol
Pharmacology information
Toxicology information
Summary of previous experiments
Chemistry, manufacturing, and
control information
• Form 1571
New indication
Significant change in marketing
A new route of administration
Dosage level change
New subject population
Changes that significantly
increase the risks associated with
use of the investigational product
The FDA will notify the PI of approval via formal correspondence containing
an IND number and a date of approval. All correspondence and original
submission materials should be maintained in the regulatory binder.
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Investigator’s Brochure
• Includes information and cautions derived from
pre-clinical research
• Serves as the official labeling for an
investigational drug prior to FDA approval;
subsequently, the approved package insert
becomes the official labeling
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Objectives
Determine Safe Dose
Range
Toxicity Levels
Pharmacodynamics
Pharmacokinetics
Dose Limiting Toxicity
(DLT)
Maximum Dose
Tolerated (MDT)
Phase I
• Investigational product is tested
in human for the first time
• Small cohort
• Closely monitored
• Healthy targets and patients
with targeted disease states
• Often Unblinded
• Uncontrolled
• Dose escalation
• If safety or efficacy concerns
arise, human research is
discontinued
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Phase II
Objectives
Determine disease
response to study
drug
Drug-drug
interaction
Efficacy at various
doses
Patient Safety
• Evaluation of safety and
disease treatment effects
• 100-300 subjects
• Specific disease
condition
• Continued research
regarding safety and less
common side effects
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Phase III
Objectives
Compare study
interventions to
standard treatment
for disease
Phase III
information used for
drug labeling
Data is analyzed and
findings are
submitted to the
FDA
• Treatment evaluation
• Thousands of subjects
• Multi-center design
• Treatment vs. Placebo
• Controlled
• Study intervention
compared to or
combined with
standard treatment
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New Drug Application (NDA)
• Submission requesting FDA approval to market
a new drug
• Review of all pre-clinical and clinical trial data
• Assess safety and efficacy
• FDA may audit sites to verify data submitted in
the NDA
• If approved, the drug can be marketed and sold
to the public under the FDA guidelines for
marketing and distribution
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Phase IV
• Post-marketing studies
• Long-term safety
• Affects on different cohorts
▫ Dosing
▫ Race
▫ Gender
• The sponsor must continue to report Adverse Events
(AEs) and finding to the FDA via MedWatch Forms
If dangerous side effects are found, the drug is taken
off the market or a Black Box may be added
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IRB Submission
• All IRB submissions are done electronically using the
institutional IRB system or a Central IRB as allowed by the
institution (such as WIRB, Quorum)
• IRB submissions will not be approved without an approved
budget from the Office of Sponsored Research (OSR)
(sequence depends on institution)
• The following documents are included in the with the IRB
submission:
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▫
▫
▫
▫
▫
Protocol
Budget (Department/Institutional requirements)
Investigator’s Brochure
Recruitment Materials
Informed Consent
Research Supplemental Submission (if applicable)
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Research Responsibilites
• Contract: Contracts analyst OSR, Coordinator,
Investigator, Sponsor
• Budget: OSR, Coordinator &/or Regulatory
specialist
• Informed Consent: Coordinator &/or
Regulatory specialist
• Regulatory: Coordinator &/or Regulatory
specialist
• IRB Submission: Coordinator &/or Regulatory
specialist
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Critical Regulatory Documents
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•
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•
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•
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•
•
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•
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•
•
CDA executed
1572
CVs for all research staff involved in the study (signed and dated within 2 years)
Medical Licenses
Protocol
Amendments
Investigator’s Brochure
Protocol Signature Pages
Critical Correspondence
Test Article Records and Drug Accountability
Delegation of Responsibility Log
IND Safety Reports
Laboratory Certifications
Laboratory Reference Ranges
Lab Director’s CV and License
Telephone Logs
Site Signature Logs
Monitoring Log
Financial Disclosures
Conflicts of Interest
Enrollment & screening logs
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The IRB: What you need to know
• You must complete CITI training prior to being
added to a protocol
• You must be added to a protocol with the IRB
prior to obtaining patient consent or doing any
protocol related tasks
• You must have documented training on each
protocol
• No study procedures can be completed prior to
obtaining informed consent
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The IRB: What you need to know
• Unanticipated Problems
If you encounter a serious event that meets the
following criteria, work with your PI to report
the SAE to the IRB:
▫ Unexpected
▫ Related or possibly related
▫ Suggests the research places subjects or others at
risk of unknown harm
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The Impact of Research
“Scientific Research has produced substantial social
benefits. It has also posed some troubling ethical problems.”
Belmont Report 1979
400 BCE
Hippocratic
Oath
1938
Food and
Drug Act
1949
International
Code of
Medical
Ethics of the
World
Medical
Assembly
1947
Nuremburg
Code
1962
KefauverHarris
Amendment
1964
Helsinki
Declaration
1966
FDS
Regulations:
21CRF
1979
Belmont
Report
1996
ICH
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The Impact of Research
• Berlin Code of Ethics: World’s first official
regulation of human experimentation, barring nontherapeutic interventions without voluntary
consent, as well as experiments on minors and
others judged vulnerable or incompetent.
• The Nuremberg Code: International code of
ethics established in response to inhumane Nazi
human experimentation during WWII. The
Nuremberg Code established four principles:
▫
▫
▫
▫
Informed Consent
Absence of Coercion
Properly formulated scientific experimentation
Beneficence towards experiment participants
35
The Impact of Research
• Kefauver-Harris Drug Amendments:
Passed to ensure drug efficacy and greater drug
safety; drug manufacturers are required to prove
to the FDA effectiveness of their products before
marketing them and tests for safety during
pregnancy are required before a drug can receive
approval for sale in the U.S. As a result, the FDA
is given closer control over investigational drug
studies and FDA inspectors were granted access
to additional company records.
36
The Impact of Research
• Declaration of Helsinki: A statement of ethical
principles stating that in medical research on
human subjects, considerations related to the
wellbeing of the human subject should take
precedence over the interests of science and society.
This document is widely considered the cornerstone
of human research ethics.
• The Belmont Report: The National Research Act
led to the Belmont Report, which outlined 3 basic
principles:
▫ Respect for persons
▫ Beneficence
▫ Justice
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Principles of The Belmont Report
Respect for persons: Informed Consent
• Individuals should be treated as autonomous
agents… capable of deliberation about personal
goals and of acting under the direction of such
deliberation
• Persons with diminished autonomy are entitled
to protection.
• Requirements to acknowledge autonomy and the
requirement to protect those with diminished
autonomy.
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Principles of The Belmont Report
Beneficence: Benefits in research should
outweigh the risks
• Do not harm the human subject.
• Maximize possible benefits.
• Minimize possible harm.
39
Principles of The Belmont Report
Justice: Equality in selection and opportunity to
participate in research
• Each person should have equal share according
to:
▫
▫
▫
▫
Individual need
Individual effort
Societal contribution
Merit
40
The Impact of Research
• International Conference on Harmonization
(ICH): Good Clinical Practice (GCP) set as the
international standard, providing public
assurance that trial subjects are protected.
41
Form 1572
The 1572 is an investigator’s
signed contract with the FDA,
agreeing to uphold federal
clinical study obligations
No investigator may participate
in an investigation until a 1572
is signed
Device studies use an
Investigator’s Agreement
Form, which is the equivalent
to the 1572
• Name and address of the
investigator
• Education, training, and
qualifications of investigator
• Address of research facilities
and clinical laboratories
• Name and address of the IRB
• Name of co-investigators and
research staff
• Protocol number and title
• Commitments
• Signature
• Date
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Form 1572
• The PI agrees to personally conduct or supervise
the described investigation
• The PI agrees to maintain adequate and accurate
records in accordance with 21 CRF 312.62 and to
make those records available for inspection in
accordance with 21 CRF 312.68
• The PI ensures that all associates, colleagues,
and employees assisting in the conduct of the
study are informed regarding their obligation to
meet all commitments of the study
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Guidelines and Regulations
• Federal Regulations
▫ Code of Federal Regulations (CFR)
 CFR Title 46 Part 46: Outlines federal policy for the protection
of human subjects in research, establishing mandates for
institutional review boards (IRBs) and additional protections
for vulnerable populations.
 CFT Title 21 Part 50: Specifies that research on human subjects
at institutions that hold Federal wide Assurances (FWAs)
requires IRB review; this CFR specifies the minimum level of
review for different types of research.
• International Guidance
▫ International Conference on Harmonization – Good
Clinical Practice (ICH GCP E6)
• Local
▫ Institutional (IRB) versus Central IRB (usually selected by
sponsor but can be WIRB, Quorum or others)
44
Institutional Review Board
The Institutional Review Board (IRB) was
established in accordance with federal
regulations governing the use of human subjects
in research.
The IRB reviews and surveys research to ensure
the protection of the rights and welfare of all
research subjects.
Investigators cannot initiate or change research
protocols until they have received IRB approval.
45
Good Clinical Practice Training
All faculty or staff listed on a protocol with the IRB must have documentation of
training (may be specific requirements at institution)
Required:
CITI Web Based Training or other similar program
Required:
GCP for Clinical Trials with Investigational Drugs and Medical Devices
(U.S. FDA focus) is suitable for individuals proposing to conduct clinical trials of
drugs and devices primarily in the U.S. and/or who would prefer a more U.S. FDAcentric curriculum.
Recommended:
Clinical Research Coordinator (CRC)
CITI Program's CRC course provides a foundational training specifically focusing on
operational and regulatory elements necessary for the ethical conduct of clinical
research, while at the same time it is specifically tailored for the needs of clinical
research professionals. It offers learners a foundation that expands beyond but is
directly connected to the Human Subjects Research (HSR) and Good Clinical
Practice (GCP) ICH training.
46
Additional Training
• Protocol specific training
▫ Expectations for clinical and research specific
procedures, such as laboratory assessments, EKG,
vitals, etc.
▫ Expectations for standardized and non-standardized
study data collection methods or assessments, such as
questionnaires
▫ Sponsor specific training for EDC, Specialty
assessments, diary training, specific assessment
devices (these may take place at Investigator meeting but most
often by additional training modules/webinars)
• Shipment of Hazardous Materials (IATA)
• Blood Borne Pathogens
47
Investigator’s Meeting (IM)
• Prior to study recruitment many sponsors hold
IM to train, cover AE and SAE reporting, lab
procedures, certify investigators and/or staff in
assessments and provide a background on the
sponsor and protocol. These may be in person
meetings or via Webinar or combined with the
Site Initiation Visit (SIV).
48
Site Initiation Visit (SIV)
• Following the IM and prior to study start-up,
sponsors will hold the SIV to train, cover AE and
SAE reporting, lab procedures, certify
investigators and/or staff in assessments, collect
regulatory documents, verify the Delegation of
Authority log and answer questions all site
personnel may have about the conduct of the
study.
49
Screening and Enrollment
The protocol will specify when a subject is considered
enrolled in a study.
• Screening and enrollment logs to be maintained and
provided to sponsor per protocol.
▫ Separate enrollment log with complete subject
identification is necessary, to be filed in regulatory
binder but not released to sponsor as it includes
subject PHI.
• Signature on informed consent before any study
related procedures are completed.
• Randomization per protocol
• Treatment dispensed per protocol (if a treatment
trial)
50
Consent Process Document
• Required Elements of Informed consent
• Information must be provided to the subject in a
language and level understandable to the subject
(7th grade level)
• Introduction
• Study involves research
• Purpose of research
• Duration of subject involvement in the study
• Description of study procedures
• Identification of any experimental procedures
• Potential risks/ discomforts
• Potential benefits to subjects or others
51
Consent Process Document
• Alternative procedures or treatments (that are already
available to the potential subject)
• Confidentiality of subject records (e.g. access to sponsor,
FDA)
• Compensation for injury and treatment in event of
emergency
• Who subject can contact
• Participation is voluntary
• New-March 7, 2012: “A description of this clinical trial
will be available on https://www.clinicaltrials.gov/ , as
required by U.S. Law. This web site will not include
information that can identify you. At most, the web site
will include a summary of the results. You can search
this web site at any time.”
52
Consent Process Document
•
•
•
•
Unforeseen risks statement
Reasons for involuntary termination
Additional costs to subject
Consequences of decision to withdraw (e.g.
impact on their health, treatment, personal
welfare etc.)
• New findings will be communicated
• Approximate number of subjects in the study
• Payments to the subject are to be included in the
document and when they will be paid (e.g.
incentive, travel costs etc.)*
53
Consent Process Document
• It is critical to document the consent process for
your site.
• Some sites include in subject EDC chart or have
a separate consent process document including
that the subject has had time to review the ICF,
all questions were answered and the subject
received a copy of the signed consent document
for their records.
• Example of a consent process document on the
next slide.
54
Consent Process Document
Patient Name:
D.O.B.
Consent Process Document:
Potential risks, benefits and side effects of protocol # _____
have been explained. Subject
understands and denies further questions. No protocol procedures were conducted prior to obtaining
consent.
Inclusion and exclusion criteria have been reviewed by PI and subject meets/continues to meet criteria for
participation.
The subject has initialed, signed and dated the appropriate informed consent documents. Patient received a
copy of the signed consent form for their records.
Consenting Site Staff’s Signature:
Date
______
Consenting Site Staff’s Printed Name: _______________________________________
Consenting Site Study PI Signature:
Date
______
Consenting Site Study PI Printed Name: _______________________________________
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Routine Monitoring visits
• Based on CRO/sponsor requirements study
monitors will be asked to come to the site
generally within 2 weeks of initial enrollment
then every 4-6 weeks. These requirements vary
from sponsor to sponsor, may be impacted by
enrollment numbers and phase of study.
• Frequency of visits may decrease in the open
extension phases of study.
56
Research Drug/Investigational Product
•
Drug storage: Investigational drugs will be stored in the appropriately secured location (i.e.
refrigerated or frozen compounds). Accurate and complete drug accountability records MUST be
maintained.
▫
Investigational drugs, which are dispensed to patients, shall be dispensed only by authorized personnel (under
the supervision of the study physician or registered nurse) and in accordance with all state and federal, and
institutional regulations as required by law.
•
Investigational Drug Disposal: Investigational drugs shall be returned or destroyed
according to the protocol and drug company policy. If destroyed on site follow your institutional
or facility policies for hazardous waste.
•
Temperature logs: All logs for drug cabinets, refrigerator and freezer must be maintained and
available for review by the sponsor or designees. Some sites use and institutional research
pharmacy and the logs are maintained there.
•
Study Drug Blind Envelopes: In a separate binder, appropriate personnel have access to the
blind envelopes for all studies. These blind envelopes are maintained until retrieval by study
monitor at closeout. Sometimes these blinds are on the I/P container itself rather than a separate
folder. They are however, available to designated study personnel in the event of an emergency.
Every effort is made to keep the studies blinded and the sponsor is notified before the blind is
broken.
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Research SOP’s
• Important to develop site specific Research
SOP’s.
• Include record retention policies, location of
offsite storage if applicable, drug destruction
policies and plan, specific location of
temperature logs and archives of these,
maintenance of equipment logs (annual
recalibration)
• Outline site specific responsibilities for research
requirements
• Disaster Plan if one is applicable
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Access for Monitors
▫ Access for monitors to patient electronic records may be based on
institutional requirements.
▫ Some will have certified copies of the patient records printed and
dated and provided by the coordinator. Other sites may actually
allow sponsor designees “read only” access to patient records.
▫ Submit requests 2-3 weeks in advance






Monitor full legal name
Date of Birth
Last four digits of Social Security Number
IRB approval letter
Department
Start date for access
▫ EPIC: 1 year (varies by institution)
▫ Powerchart: 90 days
 Signed Confidentiality Agreement
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Questions?