Transcript Slide 1

The Importance of Standard Operating
Procedures (SOPs) in Clinical Trials
The Main Objective:
• Be a GREAT clinical research site
– For the sponsor
– For your patients
– For your organization
– For your own professional development
Presentation Objectives
At the conclusion of this discussion, participants
will be able to:
– Define standard operating procedures (SOPs)
as they pertain to the clinical trial environment
– Describe key components of an SOP
– List SOPs that exist in your institution and
department that pertain to clinical research
– Understand what additional SOPs will aid in
performing high quality clinical research
– View SOPs from the perspective of the
sponsor
What are SOPs?
• Standard Operating Procedures (SOP) are:
– a set of instructions with the force of a
directive that defines or standardizes a
procedure or specific function
– an effective catalyst to drive performance
improvement and improve organizational
results
– create the level of quality and accepted
practice for a specific procedure
– the foundation of every good quality system
SOPs for Clinical Research
Clinical research SOPs are an important way
to help you follow
Good Clinical Practices
(GCPs)
What are GCPs?
• Good Clinical Practices are guidelines for
conducting sponsored clinical research
• Published by the International Conference on
Harmonization (ICH)
ICH
• International Conference on Harmonization
• ICH consists of regulatory authorities from
Europe, Japan and the United States and
experts from the pharmaceutical industry in the
three regions to discuss scientific and technical
aspects of clinical research.
• ICH is considered the authority on clinical
research theory and principles.
www.ICH.org
ICH Principles
• The guiding principles of ICH are to:
– develop scientific consensus through
discussions between regulatory and industry
experts
– assure wide consultation of draft consensus
documents through normal regulatory
channels before a harmonized text is adopted
– secure commitment by regulatory parties to
implement the ICH harmonized text
The Pharmaceutical Journal Vol 273, No. 7312, pp 24-226
ICH
• Publications of the ICH include:
– Safety management in clinical trials, including
periodic safety updates of research and
marketed drugs
– Dose response data collection
– Statistical principles for clinical trials
– Publication of the final study report
– Choice of control groups in clinical trials
– Pediatric clinical trials
– Good Clinical Practices
ICH E6: Good Clinical Practice
• Contents:
1. Glossary
2. The Principles of ICH GCP
3. Institutional Review Boards
4. Investigator
5. Sponsor
6. Clinical Trial Protocol(s)
7. Investigator Brochure
8. Essential Documents for the Conduct of a
Clinical Trial
• Get to know this document!
US regs vs. ICH?
• The ICH does not override US regulations
governing clinical research; instead they are
complimentary
– 21 CFR 312
(Requirements for an IND)
– 21 CFR 50
(Protection of Human Subjects)
– 21 CFR 56
(IRBs)
– 45 CFR 46
(HIPAA)
– 21 CFR 812
(Investigational Devices)
US regs and ICH
• Pharmaceutical and device sponsors know and
follow both ICH and federal regulations
governing clinical research
• Sponsors expect clinical sites to be familiar with
the ICH and the federal regulations
SOPs and Regulations
• SOPs are not specifically mentioned in the FDA
regulations
– HOWEVER there is guidance and regulations
that infer responsibility and SOPs formalize
investigator responsibilities.
– 21 CFR312.53 mandates that the investigator
will “ensure that all associates, colleagues,
and employees assisting in the conduct of the
study are informed of their obligations in
meeting the above commitments.”
SOPs and Regulations
• Additionally, SOPs are mentioned repeatedly in
the ICH GCP Guidelines.
• ICH GCP 2.13 -“Systems with procedures that
assure the quality of every aspect of the trial
should be implemented.”
Benefits of SOPs
• Ensures that all research conducted within the
clinical site follows federal regulations, ICH GCP,
and institutional policies to protect the rights and
welfare of human study participants
• Improves the quality of the data collected,
thereby improving the science of the study.
• Utilized as a reference and guideline as to how
research will be conducted within the clinical site
• Excellent training source for new employees
and/or fellows
SOPs for Imaging: Benefits
• Image standardization
– All technologists doing the same task in the
same way
– Reproducible camera performance
– Documentation of deviations
• Standardization of patient data
– Blood and urine samples
– Vital signs
– ECGs
Key Components of SOPs
• Description of the purpose of the procedure/task
• Background information and definitions
• Specific components to successfully perform the
task/procedure
– Required personnel to perform all aspects of
the procedure
– Appropriate patient population (as applicable)
– Required equipment, supplies, information
and/or data
Key Components of SOPs (cont.)
– Equipment settings, as appropriate and/or
necessary to acquire/process data
– Quality control procedures to assure optimal
results
– Interpretation and reporting criteria, as
necessary for consistent and uniform review
of data
• Effective date and expiration date
SOPs: An Educational Tool
• SOPs may be used as an educational tool to:
– familiarize the entire research team on the
specific tasks performed by the departments
participating in the research protocol
– educate the drug company/investigator on
regulatory guidelines and SOPs already in place
for departments such as radiology, nuclear
medicine and radiation therapy in the
performance of day-to-day procedures
– train current and new employees to assure
consistent performance of the research protocol
SOPs: Institutional Examples
• Examples of Institutional SOPs:
– Patient identification
– Patient confidentiality (HIPAA)
– Patient safety and incident reporting
– Infection control
– Hazardous waste disposal
– Use/repair of medical equipment
SOPs: Nuclear Medicine
• Examples of SOPs in Nuclear Medicine:
– receipt, administration, disposal and storage of
radioactive materials
– ALARA protocols
– Personnel monitoring
– Pregnancy protocols (patient/employee)
– Radioactive spills
– Quality control procedures
– Safety training (ie, CPR, fire extinguisher, patient
transfers)
SOPs: Nuclear Medicine (cont.)
• Examples of SOPs in Nuclear Medicine:
– Specific imaging/non-imaging protocols
• Quality control
• Patient assessment
• Patient education/preparation/discharge
• Acquisition
• Processing
• Data storage/transfer
– Adverse drug events/misadministrations
Patient Privacy SOPs
• Sometimes these get complicated with nuclear
medicine data –
– Can data go to PACs with a research code
number?
– Is the data sent to the sponsor with the
identifiers stripped?
– Is there a backup copy of identifiable data in
the department?
– Who has access to the images or biologic
data?
Patient Privacy SOPs (cont.)
• Electronic data transfer
– Firewall issues
– Patient ID issues
– May have to work with IT department
– May need administrative approval
Investigational Product SOPs
• Regulatory (NRC or state) guidelines direct the
receipt, handling, storage and disposal of
radioactive materials; however, sponsors may
not be familiar with those guidelines and
appreciate seeing SOPs to meet ICH E6 and
21CFR312 guidelines
ICH E6 : Investigational Product
4.6.3 The investigator/institution and/or a
pharmacist or other appropriate individual, who
is designated by the investigator/institution,
should maintain records of the product's delivery
to the trial site, the inventory at the site, the use
by each subject, and the return to the sponsor or
alternative disposition of unused product(s).
These records should include dates, quantities,
batch/serial numbers, expiration dates (if
applicable), and the unique code numbers
assigned to the investigational product(s) and
trial subjects.
ICH E6 : Investigational Product
4.6.3, cont. Investigators should maintain
records that document adequately that the
subjects were provided the doses specified by
the protocol and reconcile all investigational
product(s) received from the sponsor.
ICH E6 : Investigational Product
4.6.4 The investigational product(s) should be
stored as specified by the sponsor
4.6.5 The investigator should ensure that the
investigational product(s) are used only in
accordance with the approved protocol.
4.6.6 The investigator, or a person designated by
the investigator/institution, should explain the
correct use of the investigational product(s) to
each subject and should check, at intervals
appropriate for the trial, that each subject is
following the instructions properly.
21CFR312: Investigational Product
• Sec. 312.62 Investigator recordkeeping and
record retention. (a) Disposition of drug. An
investigator is required to maintain adequate
records of the disposition of the drug, including
dates, quantity, and use by subjects. If the
investigation is terminated, suspended,
discontinued, or completed, the investigator
shall return the unused supplies of the drug to
the sponsor, or otherwise provide for disposition
of the unused supplies of the drug under 312.59.
21CFR312: Investigational Product
• Sec. 312.61 Control of the investigational drug.
An investigator shall administer the drug only to
subjects under the investigator's personal
supervision or under the supervision of a subinvestigator responsible to the investigator. The
investigator shall not supply the investigational
drug to any person not authorized under this
part to receive it.
Medical Records SOPs
• Electronic? Compliant with 21CFR 11?
• Nuclear medicine reports?
• Other documents – worksheets, H&P
questionnaires?
• Radiopharmacy dosing records – integrated into
medical records?
Documentation SOPs
• 21CFR312.62 (b) Case histories. An investigator is
required to prepare and maintain adequate and
accurate case histories that record all observations
and other data pertinent to the investigation on each
individual administered the investigational drug or
employed as a control in the investigation. Case
histories include the case report forms and supporting
data including, for example, signed and dated consent
forms and medical records including, for example,
progress notes of the physician, the individual's
hospital chart(s), and the nurses' notes. The case
history for each individual shall document that
informed consent was obtained prior to participation in
the study.
Documentation SOPs
• An auditor has access to ALL records, including
nuclear medicine worksheets, film jackets, digital
copies of data
• Recordkeeping SOP: no white out, no erasures,
signature and date by individual who made the
entry, etc.
Conditions of Participation
• 42 CFR 482.53 – Nuclear Medicine Services:
If the hospital provides nuclear medicine
services, those services must meet the needs of
the patients in accordance with acceptable
standards of practice.
– a) Standard: organization and staffing. The
organization of nuclear medicine service must
be appropriate to the scope and complexity of
the services offered
Conditions of Participation
• Data acquisition must be accurate and
consistent
• Acquisition protocols must be per
sponsor’s/clinical investigator’s specifications
• Gamma camera must meet software and QC
specifications
• Data transfer must meet sponsor’s
specifications
• Patient information (demographics) must be
stripped from the final study prior to transfer;
essential acquisition/processing data must be
retained
Where do I start?
• Gather your institution’s SOPs that cover
aspects of safety and patient care
• Gather your departmental SOPs that cover
quality assurance, storage of
radiopharmaceuticals, data management,
processing of biologic samples
• Perform a gap analysis – what GCP aspects are
not currently covered by an SOP?
• Write SOPs to cover the needed areas
Sponsor Confidence Boosters
• Site personnel understanding of GCP
• SOPs that indicate quality assurance is
important to the site
• Attention to image standardization via SOPs
• Attention to documentation via SOPs
Summary
• Sponsors expect you to be familiar with ICH
GCP and the federal regulations
• Gather or develop SOPs that will provide clear,
precise instructions/directions for tasks and
conditions that are covered in the GCPs
– Institutional and departmental SOPs will be
useful
– Create documentation SOP as a way to train
all employees about appropriate recordkeeping methods
Summary
• SOPs to cover aspects of GCP are sponsor
confidence boosters
• Don’t stop at being a GOOD research site –
become a GREAT research site!
Acknowledgements
Presentation writers:
Rebecca Sajdak
Kathy Thomas
Presentation Editor:
Aileen Carey
Knowledge Assessment Writer:
xxx
VOICE application:
xxx