Clinical Medical
Resume:
SAMPLE SOPS FOR
CLINICAL INVESTIGATIONS
AT EMORY UNIVERSITY
OFFICE OF RESEARCH COMPLIANCE
WEBSITE: HTTP://WWW.ORC.EMORY.EDU/
CONTACT: ***@*****.***
DECEMBER 2009
SAMPLE SOPS: DRAFT
TABLE OF CONTENTS
Table of Contents
Introduction
Good Clinical Practice (GCP) 3
Glossary of Terms 8
Sample Standard Operating Procedures 16
CT 001 Write, Revise, Maintain Standard Operating Procedures (SOPs) 17
CT 002 Documentation Practices 19
CT 003 Training - Investigator and Clinical Research Staff 22
CT 004 Responsibilities of the Principal Investigator 25
CT 005 Responsibilities of the Research Staff, Study Task Assignment 29
CT 006 Assessments of a Study Protocol 31
CT 007 Set-up of the Study Files & Regulatory Documents Binder 35
CT 008 Management of Case History Records & Source Documents 39
CT 009 Case Report Form (CRF) Completion, Corrections, Handling queries 41
CT 010 Control & Accountability of Test Article 44
CT 011 Subject Screening and Enrollment 46
CT 012 Interactions with the Institutional Review Board (IRB) 48
CT 013 Informed Consent Process 52
CT 014 Monitoring and Audit visits 56
CT 015 Event Recording, Reporting Requirements 58
CT 016 Reporting Protocol Deviations 62
Forms
SAMPLE SOPS DRAFT FEB2009
INTRODUCTION
GOOD CLINICAL PRACTICE (GCP)
GCP at Emory covers all clinical investigations involving FDA regulated test articles using human
subjects conducted, in whole or in part, by or under the supervision of Emory University faculty, staff
or students, or using Emory University facilities, funding or other University resources.
GCPs for the investigative site are standards set by the FDA that delineate the roles and
responsibilities of clinical investigators and all key personnel involved in the Research Protocol.
Sample standard operating procedures (SOPs) are provided as a guide for clinical trials
operations. SOPs are subject to applicable regulations, i.e. HHS, FDA, HIPAA; in the event of any
conflicts between those laws or regulations and such SOPs, said laws and regulations shall control.
The aim of these SOP templates and accompanying example forms is to provide researchers a way to
standardize and simplify their organization and documentation relating to clinical trials, fostering
conformance to Good Clinical Practice (GCP) requirements in clinical research. These SOPs are
written templates that, if implemented, will permit a useful degree of uniformity in the performance of
clinical studies.
Example forms are included which should be customized.
Background: Prior to beginning any Human Subjects Research, the clinical investigator must have
acquired the appropriate knowledge and training regarding human research subject protections, the
ethical conduct of research, and applicable regulations, as well as the specific knowledge needed to
properly conduct his/her specific protocol(s). Prior to initiating work under any Research Protocol,
the clinical investigator must thoroughly read and understand the Research Protocol as well as any
informed consent and HIPAA Authorization documentation associated with the Research Protocol.
The investigator is responsible for both the welfare of subjects and the quality of the data collected
during the course of his/her clinical study. The clinical investigator and all key personnel involved in
the Research Protocol must comply with all requirements imposed by the FDA Regulations, HHS
Regulations, HIPAA Regulations and any other applicable laws and regulations. The FDA expects that
a clinical trial is conducted in accordance with Good Clinical Practice (GCP). Compliance with GCP
provides assurance that the rights, well-being, and confidentiality of trial subjects are protected and
that trial data are credible.
GCP is an international ethical and scientific quality standard for designing, conducting, recording, and
reporting trials that involve the participation of human subjects. GCP is delineated in the International
Conference on Harmonisation (ICH) guidance entitled Good Clinical Practice: Consolidated
Guideline'' (ICH-E6). The Consolidated Guideline represents the FDA s current thinking on good
clinical practices and describes the essential documents that individually and collectively permit
evaluation of the conduct of a clinical study and the quality of the data produced. The guideline is to
be followed when generating clinical data that are intended to be submitted to regulatory authorities
and should also be applied to other investigations that involve therapeutic intervention in, or
observation of, human subjects. The guidance document can be accessed on the FDA website URL:
http://www.fda.gov/downloads/regulatoryinformation/guidances/UCM129515.pdf .
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INTRODUCTION
OUTLINE OF GCP:
The rights and welfare of the individual clinical research subject must always be the paramount
consideration in conducting clinical research. Accordingly, clinical research must be conducted in a
manner that protects the rights, welfare and confidentiality of the human subject and also assures
data credibility by protecting the integrity of accurate data that has been demonstrably collected
according to the approved protocol.
1. The investigator must read the protocol and is personally responsible for:
1.1. Ensuring that an investigation is conducted according to:
1.1.1. the signed investigator statement/agreement,
1.1.2. the investigational plan (study protocol),
1.1.3. applicable regulations.
1.2. Ensuring that all persons assisting with the trial are adequately informed about:
1.2.1. the protocol,
1.2.2. the investigational product(s) (test article),
1.2.3. their trial-related duties and functions.
1.3. Protection of the rights, safety, and welfare of subjects under the investigator s care.
1.4. Control of the test articles (drugs & comparators, devices) included in the investigation.
1.5. Assuring that each subject s informed consent is obtained appropriately.
1.6. Proper delegation of authority for the conduct of various aspects of the study so that the
investigator retains control and knowledge of the study.
2. The investigator shall assure that initial and continuing review of the proposed clinical study is
performed according to the policies and procedures of the Emory University Institutional
Review Board (IRB), as well as with any other IRB that has jurisdiction.
2.1. Continuous approval from the IRB must be maintained.
2.2. All unanticipated problems involving risk to human subjects or others are promptly
reported to the IRB.
2.3. Any changes in the research activity are promptly reported to the IRB.
2.4. No changes are made in the research without IRB approval, except where necessary to
eliminate apparent immediate hazards to human subjects.
3. The investigator shall control the test articles (drugs & comparators, devices).
3.1. A test article is administered only to subjects under the investigator s personal
supervision or under the supervision of a qualified sub-investigator responsible to the
investigator
3.2. A test article is not supplied/provided to any person not authorized to receive it.
3.3. Adequate records of the disposition of the test article are maintained, including dates,
quantity, receipt, distribution to subjects, and disposition.
3.4. Investigational Drug Service (IDS) is used for drug studies to control test articles,
according to the Investigational Drug Management for Clinical Studies Emory
University Policy 7.14; access this policy at http://policies.emory.edu/7.14 . Further
information regarding use of the IDS service can be found on the OCR website at
http://www.ocr.emory.edu/Pre-Award/Investigational_Drug_Service/index.cfm .
4. The PI is responsible for submitting any reports within time periods and according to
procedures called for by:
4.1. Applicable federal, state and local regulations, including HHS, FDA and VA,
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INTRODUCTION
4.2. Emory University or applicable division or departmental policy or procedures, including
the Institutional Review Board (IRB), and Office of Clinical Research (OCR),
4.3. Contractual agreements with sponsors, collaborators, etc.
5. The investigator shall take adequate precautions to prevent theft or diversion when a drug that is
a controlled substance is used in an investigation. Minimal precautions include access/use log
and restricted access to drugs in a locked and secure storage place.
6. The investigator shall keep and maintain adequate and accurate records, including:
6.1. Case histories on each individual study subject that record all observations and other
data pertinent to the investigation.
6.2. Screening, enrollment, and informed consent documentation; demonstrating that
informed consent was obtained prior to participation in the study.
6.3. Study reports, including reports of progress, safety, financial disclosure and final
completion.
6.4. Records retention as required.
6.4.1. Consult Emory records retention schedule; see http://records.emory.edu/ .
6.4.2. FDA regulation requires an investigator to retain records a minimum of two years
after the close of the study or after the records are no longer required to support a
drug or marketing application, whichever is longer.
6.4.3. Contract commitments must be met.
6.4.4. Consider transferring records to the Sponsor for contractual retention requirements
that exceed FDA or Emory records retention schedules.
6.5. Reconcile ownership conflicts during study set up.
FDA requires the clinical investigator to retain records.
Emory considers research records to belong to the university.
Departmental guidance should be established and followed, especially if the investigator
leaves the university before the scheduled destruction of records.
6.6. Record transfer or record destruction should be verified and documented.
7. The investigator shall permit properly authorized persons such as governmental officials,
Sponsor representatives or internal quality reviewers, to have access to copy, and verify records
or reports made by the investigator.
7.1. Notice of such inspectional privileges shall be included in the Informed Consent form
and HIPAA Authorization form.
7.2. The investigator is not required to divulge subject names to government inspectors
unless there is a specific government request for this information; e.g. for the records of
particular individuals require a more detailed study of the cases, or there may be reason
to believe that the records do not represent actual case studies, or do not represent actual
results obtained.
8. An MD must be designated as responsible for all trial-related medical decisions. Medical
decisions must be made by a qualified person permitted by state licensure laws to make or enact
such decisions. The investigator should:
8.1. Ensure that adequate medical care is provided to a subject for any adverse events related
to the trial, during and as followup to a subject's participation.
8.2. Inform a subject when medical care is needed for intercurrent illness(es) of which the
investigator becomes aware.
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INTRODUCTION
8.3. Inform the subject's primary physician about the subject's participation in the trial if the
subject agrees to the primary physician being informed, and has signed a HIPAA
Authorization form permitting such disclosure.
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References:
Conducting Clinical Trials within the Emory University School of Medicine (EUSOM),
access at link called User Manual for Clinical Trials from
http://www.ocr.emory.edu/index.cfm .
Emory University Institutional Review Board Policy & Procedures (IRB P&P)
http://www.irb.emory.edu/researchers/formstools/docs/other/PoliciesAndProcedures.pdf .
Compliance Program Guidance Manual for FDA Staff Compliance Program 7348.811
Bioresearch Monitoring: Clinical Investigators; especially Part III Inspectional
http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/ucm133562.htm .
Device Advice, FDA Center for Devices and Radiological Health (CDHR), at
http://www.fda.gov/cdrh/devadvice/ .
Good Clinical Practice in FDA-Regulated Clinical Trials, at
http://www.fda.gov/oc/gcp/default.htm .
Office for Human Research Protections at http://www.hhs.gov/ohrp/ .
Form FDA 1572 Statement of Investigator, at
http://www.fda.gov/opacom/morechoices/fdaforms/FDA-1572.pdf .
21 CFR 50 Protection of Human Subjects
21 CFR 54 Financial Disclosure by Clinical Investigators
21 CFR 56 Institutional Review Boards
21 CFR 312 --- Investigational New Drug Application
21 CFR 314 --- Applications for FDA Approval to Market a New Drug
21 CFR 809 --- In Vitro Diagnostic Products for Human Use
21 CFR 812 --- Investigational Device Exemptions
21 CFR 814---Premarket Approval of Medical Devices
45 CFR 46 Protection of Human Subjects
45 CFR 160 --- General Administrative Requirements
45 CFR 164 Security and Privacy
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm
ICH E2A FDA Guideline for Industry Clinical Safety Data Management: Definitions
and Standards for Expedited Reporting; March 1995
ICH E2C FDA Guideline for Industry Clinical Safety Data Management: Periodic
Safety Update Reports for Marketed Drugs; November 1996
ICH E6 FDA Guidance for Industry Good Clinical Practice: Consolidated Guidance;
1996
http://www.ich.org/cache/compo/276-254-1.html
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INTRODUCTION: GLOSSARY OF TERMS
GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
Adverse Event or Any untoward medical occurrence in a clinical investigation subject;
AE
Adverse Effect an AE does not necessarily have a causal relationship with the study
treatment. An AE can therefore be any unfavorable and unintended
Is this a UP now? Or
sign (including an abnormal laboratory finding), symptom, or disease
keep AE and add UP?
temporally associated with testing the investigational product,
whether or not related to the product. (ICH-E2A)
ALCOA Attributable, Legible, Contemporaneous, Original, Accurate,
expectations of the FDA to demonstrate acceptable data quality.
Case History Records The information comprising an individual case, includes the Case
Report Form (CRF) and supporting data such as signed/dated
Informed Consent Forms, research notes and protocol test records;
may also include physician progress notes, nurses notes, hospital
charts, medical records, etc.
CRF Case Report Form A printed, optical, or electronic document designed to record all of
the protocol-required information to be reported to the Sponsor on
each trial subject.
A CRF is used to record all relevant individual subject or study
patient data. The Sponsor will use this data to perform statistical
analysis; the resultant analyses are included in the medical report.
The CRF is designed by the Study Sponsor, possibly in collaboration
with the Investigator, and is based on the Study Protocol.
Clinical Investigation Any experiment in which a Test Article is administered or dispensed
to, or used, involving one or more human subjects. An experiment is
any use of a Test Article except for the use of a marketed product in
the course of medical practice. (FDA)
Clinical trial: A biomedical or behavioral research study of human subjects
that is designed to answer specific questions about biomedical or
behavioral interventions (drugs, treatments, devices, or new ways of using
known drugs, treatments, or devices). (NIH definition)
Note throughout these CT SOPs clinical investigation, study,
and clinical trial may be used interchangeably.
CI Clinical Investigator See Investigator
CRC Clinical Research Assists the Principal Investigator (PI) in the setup and conduct of a
Coordinator clinical trial, working at a clinical research site under the immediate
direction of a PI and whose research activities are conducted under
Good Clinical Practice (GCP) Guidelines. Refer to the online user
manual for research personnel Conducting Clinical Trials within the
Emory University School of Medicine found on the OCR website
http://www.ocr.emory.edu/Education_&_Outreach/OCR_User_M
anual/index.cfm .
CT Clinical Trial See Clinical Investigation
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INTRODUCTION: GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
CTA Clinical Trial Agreement The CTA defines the responsibilities of each party with respect to
specific trial-related duties, indemnity and financial matters: what
costs will be covered, and when and how payments will be made.
The CTA must be processed through and signed by appropriate
individuals in the Office of Sponsored Programs. Individual PIs
are not authorized to enter into CTAs or contracts on behalf of
Emory University. For sponsored trials, a CTA signed between
Emory University and the sponsor of a clinical trial is required prior
to subject enrollment, and should be in place before expenditure of
funds.
CFR Code of Federal The codification of the general and permanent rules published in the
Regulations Federal Register by the executive departments and agencies of the
Federal Government. It is divided into 50 titles that represent broad
areas subject to Federal regulation, updated once each calendar year.
FDA and DHHS/Public Welfare regulations are found in 21 CFR
and 45 CFR, respectively.
CDA Confidential Disclosure A legal contract between the signing parties that outlines the
Agreement confidential materials the parties wish to share for the purpose(s)
specified. CDAs can restrict all parties in their use of the materials
provided, or they can only restrict a single party. CDAs are also
known as non-disclosure agreements or confidentiality agreements.
Confidential information is generally a trade secret and means
Confidential
information that derives actual or potential value from not being
Information
generally known to, and not being readily ascertainable by, other
persons who could obtain economic value from its disclosure or use.
Confidential information may include intellectual property, technical
or nontechnical data, a formula, pattern, compilation, program,
device, method, technique, drawing, process, financial data, financial
plans, product plans, or other information which is not commonly
known by or available to the public and is the subject of reasonable
efforts to maintain its secrecy.
CRO Contract Research A person that assumes one or more of the obligations of a Sponsor,
Organization as an independent contractor to the Sponsor.
CV Curriculum Vitae A written description of an individual s work experience, educational
background, and skills; may include a list of publications,
presentations, awards, honors, affiliations and other details. Refer to
http://www.medicine.emory.edu/faculty_staff/faculty/promotions/cv.cfm
or http://www.med.emory.edu/dean/docs/Standard_CV_Template.pdf .
DHHS Department of Health One of the largest federal agencies, the Department of Health and
and Human Services Human Services is the principal agency for protecting the health of
all Americans. DHHS responsibilities include public health,
biomedical research, Medicare and Medicaid, welfare, social services,
and more. DHHS agencies include FDA, NIH and the CDC.
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INTRODUCTION: GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
Device A device is intended to affect the structure or any function of the
body; it does not achieve its primary intended purposes through
chemical action or metabolism within or on the body.
A medical device is a physical item (an instrument, apparatus,
implement, machine, contrivance, implant) or an in vitro reagent, or
other similar article that is intended for use in the diagnosis of
disease or other conditions, or in the cure, mitigation, treatment or
prevention of disease. Medical devices range from simple tongue
depressors and bedpans to complex programmable pacemakers with
micro-chip technology and laser surgical devices.
Drug A drug is a chemical substance that is intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of disease, and
substances, other than food, intended to affect the structure or any
function of the body.
Investigational new drug or investigational drug means a new
drug that is used in a clinical investigation and includes a biological
product that is used in vitro for diagnostic purposes.
ICH defines investigational product as a pharmaceutical form of
an active ingredient or placebo being tested or used as a reference in
a clinical trial, including a product with a marketing authorization
when used or assembled (formulated or packaged) in a way different
from the approved form, or when used for an unapproved
indication, or when used to gain further information about an
approved use.
EHSO Environmental Health Emory University EHSO is chiefly responsible for risk assessment
and Safety Office and hazard mitigation from biological, chemical or radiological
sources.
EUSOM Emory University http://www.med.emory.edu/
School of Medicine
FDA Food and Drug The FDA is the federal agency responsible for protecting the public
Administration health by assuring the safety, efficacy, and security of human and
veterinary drugs, biological products, medical devices, food supply,
cosmetics, and products that emit radiation; and that these products
are honestly, accurately and informatively represented to the public.
GCP Good Clinical Practice An internationally recognized standard for the design, conduct,
performance, monitoring, auditing, recording, analysis, and reporting
of clinical trials that provides assurance that the data and reported
results are credible and accurate, and that the rights, integrity, and
confidentiality of trial subjects are protected.
HHS Health and Human Shortened form of DHHS.
Services
Health Information: Any information whether oral or recorded in any form that is created
or received by the Emory Covered Component that relates to an
individual s past, present or future physical or mental health or to the
payment for such health care.
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INTRODUCTION: GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
HIPAA Health Insurance Privacy rules promulgated by the US government directing health
Portability and care entities (covered entities) to establish procedures to ensure the
Accountability Act security, integrity, privacy and authenticity of health information and
to safeguard its access and disclosure.
Individually Identifiable Health Information including demographic information that
Health Information identifies an Individual or with respect to which there is a reasonable
basis to believe the information can be used to identify the
Individual.
ICF Informed Consent Form A statement explaining the study to a potential subject, including the
risks entailed in participation. The ICF is used to document the
subject s voluntary agreement, based upon adequate knowledge and
understanding of relevant information, to participate in research or
to undergo a diagnostic, therapeutic, or preventive procedure.
Also called Informed Consent Document (ICD).
IRB Institutional Review An appropriately constituted group that has been formally designated
Board to review and monitor research involving human subjects; having the
authority to approve, require modifications in, or disapprove
research. This group review serves an important role in the
protection of the rights and welfare of human research subjects.
IDS Investigational Drug Emory University IDS, located at the Emory University Hospital and
Service Clinic A.
A clinical investigator is any listed or identified investigator or sub-
Investigator:
investigator who is directly involved in the treatment or evaluation
of research subjects.
Clinical investigator
CI
The principal investigator: is the individual responsible for the
conduct of a clinical trial at a trial site, under whose immediate
Principal investigator
PI
direction the test Article is administered or dispensed to a subject.
If a trial is conducted by a team of individuals at a trial site, the
Co-investigator
Co-I or
investigators are co-investigators. The principal investigator is the
Co-PI responsible leader of the team. Co-investigators sign a Form FDA
1572 or the investigator agreement with the Sponsor and each co-
investigator is individually held responsible for all investigator
responsibilities, as agreed to by signing on the 1572 or investigator
agreement.
Sub-investigator includes any individual member of the clinical trial
Sub-investigator
Sub-I
team designated and supervised by the investigator at a trial site to
perform critical trial-related procedures and/or to make important
trial-related decisions (e.g., associates, residents, research fellows).
A sub-investigator is listed on the 1572, but does not sign it.
SI Sponsor Investigator See Sponsor-investigator
Clinical investigators sign investigator agreements/statements that
Investigator
attest to their knowledge of and agreement with their
Agreement/Statement
responsibilities under FDA regulations as researchers. Drug or
biologics trials use Form FDA 1572 (investigator statement) for
this purpose and device trials use an investigator agreement.
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INTRODUCTION: GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
A clinical trial developed by the investigator and the investigator is a
IIT Investigator Initiated
Sponsor-investigator.
Trial
Those persons associated with a specific clinical investigation whose
Key personnel
assigned duties may include contact with subjects/research
volunteers; activities that may affect subject welfare or study
compliance; or impact data integrity.
An individual or judicial or other body authorized under applicable
LAR legally-authorized
law to consent on behalf of a prospective subject to the subject s
representative
participation in the procedures involved in the Research. [45 CFR
46.102(c), 21 CFR 50.3(l)]
Monitor A monitor oversees the progress of the study on behalf of the
Sponsor; ensuring that the study is conducted, recorded and reported
according to the study protocol, SOPs of the Sponsor, GCP and
regulatory requirements. The monitor s main role is to help ensure
proper study conduct and the timely generation and collection of
quality data for the Sponsor, generally accomplished by routine
inspection/monitoring of the study site.
Except for an investigator-initiated study under the direction of a
Sponsor-investigator, the monitor should be independent of the
investigative staff conducting the research at the site or institution,
and should not be employed or supervised by the investigative site or
the institution. Clinical Research Associate (CRA) is the standard
industry term for the monitor (distinct from the Emory University
HR job description for Clinical Trial Associate ).
OCR Office of Clinical OCR is part of Emory University s Office of Research
Research Administration. The mission of the OCR is to organize and enhance
operational processes that support the efforts of the clinical research
team and to facilitate the timely initiation, execution, management
and completion of clinical trials at Emory.
OGCA Office of Grants and The Office of Grants & Contracts, among other things, provides the
Contracts ( at Emory central oversight for the post-award fiscal activities of all grants and
University) contracts and maintains the labor and effort reporting systems.
OSP Office of Sponsored Collaborates with the Emory community to identify, obtain and
Programs (Emory) administer extramural funding in support of the University mission.
NIDPOE Notice of Initiation of A NIDPOE letter informs the recipient clinical investigator (CI) that
Disqualification FDA is initiating an administrative proceeding to determine whether
Proceedings and the CI should be disqualified from receiving investigational products.
Opportunity to Explain FDA may issue a NIDPOE letter when it believes the CI repeatedly
or deliberately violated FDA's regulations governing the proper
conduct of clinical studies involving investigational products, or
submitted false information to the Sponsor.
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INTRODUCTION: GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
P&P Policy and Procedures So called when a university, departmental or other unit s policy is
accompanied and supported by standard operating procedures. The
procedures may be requisite approved procedures requiring
adherence or may be template/example procedures that are designed
as guidance or recommended practice. The policy should clearly state
if accompanying Procedures are for guidance.
PI Principal Investigator See Investigator
PHI Protected Health Certain Individually Identifiable Health Information created,
Information transmitted or maintained by a covered entity.
Protocol A document that describes the objective(s), design, eligibility
requirements of subjects, methodology, statistical considerations, and
organization of a trial; for these SOPs includes the protocol and the
protocol amendments.
Protocol Deviation Any noncompliance with the protocol, good clinical practices,
regulatory or institutional requirements.
Regulatory Documents A study file created for each study containing study specific
Binder (Reg. Binder) information relating to the overall study, in contradistinction to case
history documentation. Aka Critical Documents Binder,
Essential Documents Files
Research A systematic investigation, including research development, testing
and evaluation, designed to develop or contribute to generalizable
knowledge. (HHS definition)
FDA has defined Clinical Investigation to be synonymous with
Research .
SAE Serious Adverse Event Any untoward medical occurrence that results in any of the following
outcomes: death, a life-threatening adverse experience, inpatient
hospitalization or prolongation of existing hospitalization, a
persistent or significant disability/incapacity, or a congenital
anomaly/birth defect.
Source Data All information in original records and certified copies of original
records of clinical findings, observations, or other activities in a
clinical trial necessary for the reconstruction and evaluation of the
trial. Source data are contained in source documents, either original
records or certified copies.
Source Documents Original documents, data, and records (e.g., hospital records, clinical
and office charts, laboratory notes, memoranda, subjects diaries or
evaluation checklists, pharmacy dispensing records, recorded data
from automated instruments, copies or transcriptions certified after
verification as being accurate and complete, microfiches,
photographic negatives, microfilm or magnetic media, x-rays, subject
files, and records kept at the pharmacy, at the laboratories and at
medico-technical departments involved in the clinical trial).
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INTRODUCTION: GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
Sponsor An individual, company, institution, or organization that takes
responsibility for and initiates a clinical investigation.
The role of Sponsor is NOT related to funding or financial support.
SI Sponsor-Investigator An individual who both initiates and conducts, alone or with others,
a clinical trial, and under whose immediate direction the
investigational product is administered to, dispensed to, or used by a
subject. The term does not include any person other than an
individual (it does not include a corporation or an agency). The
obligations of a Sponsor-investigator include both those of a
Sponsor and those of a principal investigator.
SOP Standard Operating Written documents that describe the routine procedures to be
Procedure followed for a specific operation, analysis, or action. Consistent use
of an approved SOP ensures conformance with organizational
practices, reduced work effort, reduction in error occurrences, and
improved data comparability, credibility, and defensibility. SOPs also
serve as resources for training and for ready reference and
documentation of proper procedures.
SOP may alternatively be called a Procedure, as in Policy and
Procedures .
Subject An individual who is or becomes a participant in research, either as a
recipient of the test article or as a control, or on whose specimen an
investigational device is used. A subject may be in normal health or
may have a medical condition or disease.
Also called Human Subject, Study Patient, and Research
Subject .
Test Article The object of an investigation for human use subject to FDA
regulations: that drug, biological product, medical or investigational
device, or the study control, used in a clinical investigation. The
term test article includes placebos and comparators
identified in the study protocol, as well as the investigation
product.
UP Unanticipated problem An event not previously identified involving risk to the participant or
others. (Refer to IRB P&P 64.)
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INTRODUCTION: GLOSSARY OF TERMS
ACRONYM TERM DEFINITION
Witness or Someone whose signature attests that the subject has provided
consent of their own free will and has been fully informed of the
Impartial Witness
study. The best witness is a subject s friend or family member who
has been present while the study was being explained to the subject.
A witness must have no vested interest in the study.
Alternatively, a witness signature may attest only to subject signature,
in which case this limited role of the witness must be clearly stated.
OR
A person, who is independent of the trial, who cannot be unfairly
influenced by people involved with the trial, who attends the
informed consent process if the subject or the subject s legally
authorized representative cannot read, and who reads the informed
consent form and any other written information supplied to the
subject. (ICH E6 1.26)
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SAMPLES OF STANDARD OPERATING PROCEDURES
SAMPLE STANDARD OPERATING PROCEDURES
The SOPs presented in this guide are intended to provide
examples of clinical trial SOPs.
PIs and/or clinical trial units are strongly encouraged to prepare
custom SOPs to substantiate clear and consistent workflow
throughout a human research study.
In the event of a conflict, applicable laws, regulations or approved
Emory University policies and procedures will take precedence
over departmental or study-specific SOPs.
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SAMPLE SOPS DRAFT
CT 001 WRITE, REVISE, MAINTAIN STANDARD OPERATING PROCEDURES (SOPS)
PURPOSE: To provide instructions to produce, approve, control, and revise Standard Operating
Procedures (SOPs).
SCOPE: This SOP delineates systematic process activities and functions for Emory University unit in
compliance with Good Clinical Practices (GCP) requirements for the management and coordination
of clinical trial operations. It applies to unit personnel engaged in clinical trial research,
administration or management.
Procedure:
1. An SOP may be initiated or revised based upon need. Revisions may respond to changes in
governmental regulations or guidelines, to Emory research practice or policy, or to improve
clarity or ease of use.
1.1 Any qualified person may prepare a draft SOP for consideration.
1.2 Anyone may propose changes to an existing SOP; users are encouraged to make
recommendations.
2. An SOP is adopted as of the Effective Date shown on each SOP, after obtaining the approval
signatures.
3. Investigators, and affiliated research and administrative staff will sign a training log
documenting their training on relevant SOPs. The training log should specify topics and SOPs
covered.
4. Departmental, Divisional or Unit SOP:
4.1 Local SOPs must clearly delineate the scope of the SOP, including who is covered and
what activities are affected.
4.2 Any user may submit a request for change, modification or revisions of an SOP to the
office or unit having approved the SOP.
4.3 Initial versions and any revisions to unit SOPs must be approved by a Unit Manager or
Department/Division Head. The second approver would generally be familiar with the
unit s research and with good clinical practice, i.e. a clinical investigator, a unit business
administrator or research administrator.
4.4 Study Specific SOP should be approved by at least two people, including the Principal
Investigator. The second approver would generally be a member of the research team,
i.e. the research nurse or clinical research coordinator.
4.5 Departmental or protocol specific SOPs may be maintained and kept available by the
department research administrator or the clinical research coordinator.
5. SOP maintenance:
5.1 Historical records of the SOPs must be maintained, so that a copy of each SOP
version, whether it has been revised, superseded, or terminated, will be retrievable.
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SAMPLE SOPS DRAFT
5.2 SOPs should be protected in order to assure the current version is in use. The official
version is the version containing the signature approvals and may be either hardcopy
or electronic file.
5.3 Upon revision, a consecutive revision number is assigned, and the version number
placed in the SOP footer.
5.4 Local (unit or study specific) SOPs may be reviewed at any time for compliance or
quality assurance purposes.
RESPONSIBILITY MATRIX
Responsible Person / Unit Action for CT Local/Departmental SOPs
Review and approve departmental CT SOPs.
Department or Division or Unit head
Ensure compliance within department to SOPs.
Maintain current and historical records of
departmental CT SOPs.
Departmental Research administrator
Make available current versions of departmental
or designee
SOPs to users, assure that obsolete versions are
archived.
Responsible Person / Unit Action for CT local/protocol specific SOPs
Principal Investigator Review and approve protocol specific SOPs.
Write and/or review protocol specific SOPs for
accuracy and effectiveness.
Clinical Trial Coordinator or designee Maintain SOPs.
Assure current version is available to users.
Responsible Person / Unit Action for All CT SOPs
Any qualified person may write an SOP.
Follow applicable SOPs.
All Clinical Trial Personnel,
Notify, in writing or by email, the SOP owner or
Research Team members
keeper upon observation of a need for update or
revision to the SOP.
RELATED SOPS:
none
RELATED FORMS:
FORM CT-01 SOP TEMPLATE
Implementation/Revision Dates:
Last Review Date:
Approval Signatures:
Effective Date:
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SAMPLE SOPS DRAFT
CT 002 DOCUMENTATION PRACTICES
PURPOSE: To encourage authenticity and the production of quality data.
SCOPE: This SOP covers all source data and source documents supporting human subject studies,
especially manual records (paper records / hard copies) such as entries to the Case Report Form. It
affects all personnel involved in recording, correcting or keeping information, either hard copy
documents or electronic files, supporting a study using human subjects.
PROCEDURE
1. Source documents.
1.1 Information must be recorded by authorized study personnel.
1.2 All blanks of a form should be filled in.
1.3 If original records are damaged or obliterated, those records shall be retained when
possible with the reconstruction of the record, including an explanation and supervisory sign-
off.
2. Data must meet quality attributes (ALCOA) to be acceptable, including:
Attributable: Entries shall be signed or initialed by the entrant.
Legible: All information/entries must be clear and readable.
Contemporaneous: Promptly record activities and results, date the signature or initials
at the time the entry is recorded.
Original: The first record of an event or data collection is source data.
Accurate: Records must be true values given with reasonable precision.
2.1 All data entries must be traceable to an individual.
Data entry must be signed or initialed.
Signature or initials must always be dated at the time of entry.
2.2 Information should be recorded in indelible ink.
The record should permit copying; consistent use of a colored ink rather than black
ink may help distinguish a copy from an original.
Neither pencils nor erasable ink pens should be used.
3. All activities must be recorded. Examples include:
Maintain telephone logs, including communications with subject, monitor or Sponsor.
Verify data or document reviews with reviewer s initials, and date of review.
Maintain records of research team meetings.
4. Corrections shall not alter or obscure an earlier entry.
4.1 Original entry must remain legible.
Do not make erasures.
Do not use correction fluids ( white-out ).
Do not over-write an entry.
Do not use pencil.
4.2 To make a correction to a hard copy:
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SAMPLE SOPS DRAFT
Cross out the wrong entry with a single line that keeps the first entry legible.
Write the correct entry near the wrong entry, or indicate location of correction if space
is limited.
Initial the correction.
Date the correction.
Explain the correction (if necessary).
Any later corrections (those not made the date of the original entry) to a record must
be explained.
Any corrections not made by the original author/entrant must be explained.
4.3 Electronic source records are subject to FDA rules, and must maintain a valid audit
trail.
5. Data entry must be performed by authorized study personnel, and the meaning of a signature
must be indicated or correlated to the entry.
5.1. Signature meaning may be indicated by statement:
5.1.1. An example of signature meaning indicated by statement is that of the informed
consent form stating If you're willing to volunteer for this research, please sign
below : the research subject s signature on an informed consent form means they
have volunteered to participate in the study.
5.2. Signature meaning may be indicated through job descriptions, team organization &
responsibilities, or study specific delegation of tasks. (refer to Sample Form 02 Study
Responsibilities Log, Examples ) Examples of signature meaning indicated by job
description and/or by team responsibilities could be:
5.2.1. Principal Investigator signature would always mean that the material has been
reviewed & approved, or reviewed & corrective action instituted as indicated, by PI.
5.2.2. CRC or Research Nurse signature or initials on a CRF would indicate that the person
signing has performed the task (such as taking/recording vital signs) or has
accurately transcribed data (such as laboratory values) received for the entry, per the
study responsibilities assignment log.
RESPONSIBILITY MATRIX
Responsible Person/Unit Action
Internal auditors or inspectors Review source data and source documents for GCP
compliance/ALCOA.
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