Get documents about "ELIGIBILITY CHECKING
Shared by: HC120727103235
-
Stats
- views:
- 0
- posted:
- 7/27/2012
- language:
- pages:
- 27
Document Sample
DFCI QACT
December 22, 2003
DANA-FARBER/HARVARD CANCER CENTER
DFCI QUALITY ASSURANCE OFFICE FOR CLINICAL TRIALS (QACT)
POLICIES AND PROCEDURES MANUAL
December 22, 2003
1
DFCI QACT
December 22, 2003
TABLE OF CONTENTS
I. INTRODUCTION AND PURPOSE ……………………………………………. 4
II. SCOPE ………………………………………………………………………… 4
III. FUNCTIONS OF THE QACT ........................................................................... 4
IV. JOB DESCRIPTIONS ……………………………………………………………….. 5
V. PATIENT ENROLLLMENT IN CLINICAL TRIALS
Prospective Patient Registration ……………………………………… 7
Retrospective Patient Registrations ……………………………………… 11
Development of Eligibility Checklists ……………………………………… 11
Eligibility Checking Process ……………………………………… 11
Consent Checking Process ……………………………………… 12
Randomization Process ……………………………………… 12
Phase I Dose-Escalation Trials ……………………………………… 12
Non-Protocol Standard Treatment Registration ……………………………. 13
DF/PCC Network Affiliate Registration ……………………………………… 13
Industry-Led & Cooperative Group Registrations ……………………………. 13
Non-Patient Volunteer Registration ……………………………………… 13
Electronic Confirmation of Enrollment ……………………………………… 14
After-Hours Registration ……………………………………… 14
The Oncology Protocol System ……………………………………… 14
VI. PATIENT REMOVAL FROM PROTOCOL/NON-PROTOCOL TREATMENT….. 15
VII. PROTOCOL CLOSURE ……………………………………… 15
VIII. PROTOCOL COMPLETION/TERMINATION .…………………………… 15
IX. REPORTS AVAILABLE FROM THE QACT …………………………… 16
X. ACTIVE PROTOCOL ACCRUAL MONITORING…………………………… 16
XI. DATA COLLECTION ……………………………………… 16
The Forms Design Process ……………………………………… 16
Data Collection onto CRFs ……………………………………… 16
XII. COMPUTERIZATION OF DATA
Data Requests …………………………………………………………………. 18
Incomplete Forms/ Missing Forms / Data Queries ………………..… 19
XIII. DOCUMENTATION AND STORAGE OF DATA
Documentation Procedure ………………………………………………. 19
Storage Procedure ………………………………………………………… 19
XIV. DATA MONITORING PROGRAM ……………………………………… 20
2
DFCI QACT
December 22, 2003
XV. CLINPOC
Membership …………………………………………………………………… 22
Accrual Monitoring Program……….……………………………………………… 23
XVI. INTERNAL AUDITING
Phase I and II Data and Safety Monitoring Board ……………………… 25
Phase III Data and Safety Monitoring Committee ………………………………. 25
Independent Response Review ………………………………………………….. 25
XVII. HIPAA RESEARCH SUBCOMMITTEE ………………………………………… 26
XVIII. NCI INVESTIGATOR 1572 RENEWAL ………………………………………… 26
Staff Updates………………………………………………………………………… 27
XIX. RESEARCH LISTSERV …………………………………………………………… 27
3
DFCI QACT
December 22, 2003
INTRODUCTION AND PURPOSE
The Quality Assurance Office for Clinical Trials (QACT) at the Dana-Farber Cancer Institute
(DFCI) was established in 1986 as the Quality Control Center (QCC). The QCC was charged
with creating a standardized data management system for clinical trials. Over time, the role of the
QCC has expanded to include a variety of tasks, such as registering subjects to clinical trials,
developing case report forms (CRFs), generating frequency and descriptive summaries for
investigators, and generating vital statistical reports for DFCI and the organizations with whom
DFCI has partnered.
In 1997 Dana-Farber/Partners Cancer Care (DF/PCC) was established. This development united
Dana-Farber Cancer Institute with Brigham and Women’s Hospital (BWH) and Massachusetts
General Hospital (MGH) as one comprehensive adult oncology center. In 2000, Beth Israel
Deaconess Medical Center (BIDMC), Children’s Hospital (CH) and the Harvard Schools of
Medicine and Public Health joined with DF/PCC to form Dana-Farber/Harvard Cancer Center
(DF/HCC). As a result, the DF/HCC Clinical Trials Support system was established, and the
QCC was renamed the Quality Assurance Office for Clinical Trials (QACT). The QACT has been
designated as the central facility for coordinating clinical trials across these multiple institutions.
The QACT has played an important role in the vast clinical trials activities across DF/HCC. For
example, in the year 2001, the QACT maintained 496 open protocols and enrolled 5,625 subjects
to protocols.
SCOPE
The QACT is responsible for review of systems for clinical trials that are conducted across
DF/HCC institutions. The QACT reports to senior management on the status of clinical research
management, through the Director of Clinical Trials Support to the Vice-President for Research at
DFCI. The Clinical Investigations Policy and Oversight Committee (CLINPOC) has oversight of
the functions of the QACT.
FUNCTIONS OF THE QACT
Specific QACT responsibilities include the following:
1. Registration of subjects on clinical trials
Up-front registration of patients to all therapeutic trials and selected ancillary trials
Development of eligibility checklists
Eligibility and consent checking
Randomization of patients to treatment arms, when necessary
Monitoring of phase I, dose escalation studies
Protocol accrual monitoring
Providing statistics for DF/HCC
2. Data computerization and QC of oncology protocols initiated within DF/HCC
Case Report Form design
Database table design and maintenance
Development of protocol specific QC procedures to maintain data integrity
Maintenance of database documentation
Report preparation
Clinical trial data monitoring program
4
DFCI QACT
December 22, 2003
3. Clinical Trial Auditing
Performance of approximately 40 audits per year for ongoing clinical trials
Presentation of final audit results to CLINPOC
Training to improve protocol compliance
4. Meeting / Project Coordination
CLINPOC
Clinical Trials Operations Committee
Health Insurance Portability and Accountability Act (HIPAA) Research Subcommittee
Data and Safety Monitoring Committee (DSMC) for High Risk Phase I and II Trials
Data and Safety Monitoring Board (DSMB) for Phase III Trials
Independent Response Review
5. Central management of investigator 1572 submissions to NCI
6. Management of a master Research Listserv for dissemination of information to DF/HCC
clinical research staff
7. Participation in regular training programs that target DF/HCC clinical research staff
JOB DESCRIPTIONS
Director/Quality Assurance Officer for Clinical Trials (1.0 FTE)
The Director of the QACT oversees the clinical trial management process at DFCI and DF/HCC.
Her duties include protocol review, grant and budget management, oversight of all systems
related to protocols, and supervision of QACT staff. The Director also prepares for external
audits conducted by the Food and Drug Administration (FDA) and the National Cancer Institute
(NCI) as necessary.
Assistant Director (2.0 FTE)
The two Assistant Directors directly supervise the QACT staff. One Assistant Director works
closely with the study teams to assess data collection methods, coordinate projects and produce
necessary reports. She sits on the IRB and identifies new protocols for data collection at the
QACT. In addition, she oversees the Data Analysts and database maintenance and the Clinical
Trial Data Monitoring Program and manages the Childhood ALL Web Site for the DFCI/ALL
consortium. The second Assistant Director directs the DF/HCC Clinical Trial Audit Program,
oversees the overall coordination of the Data and Safety Monitoring Boards and various other
projects. She also participates in internal audits, as necessary.
Protocol System Coordinator (1.0 FTE)
The Protocol System Coordinator manages the Protocol Registration System including
computing, collection, maintenance and dissemination of patient registration and protocol
information. She compiles and distributes protocol and statistical reports. Additionally, she
manages several databases relating to protocol registration and QACT administrative data. In
2001, 496 open clinical trials accrued 5,625 subjects. These trials included therapeutic and
ancillary protocols, and participants included adults and children.
Protocol Registrar (2.0 FTE)
The Registrars develop patient eligibility checklists independently or in conjunction with study
teams. They enroll and randomize patients, which involves interacting with many other
departments within DFCI and DF/HCC, such as the Research Pharmacy and Nursing
Departments. They monitor accrual of phase I dose escalation studies. Their checks include the
consent form for correct IRB-approved version, completeness and appropriate signatures. The
5
DFCI QACT
December 22, 2003
protocol registration system links with chemotherapy-order entry (COE) system, requiring
immediate response time to registration issues.
Administrative Coordinator (2.0 FTE)
One Administrative Coordinator organizes monthly CLINPOC meetings. She assists the Director
with various administrative tasks such as coordinating weekly Clinical Trials Operations
Committee (OPs) meetings and bimonthly HIPAA Research Subcommittee meetings.
Additionally, she coordinates the annual completion of NCI 1572 forms by DF/HCC investigators
involved in clinical research. She works with Risk Management and Individual DF/HCC
institutions to provide monthly updates of newly hired or terminated staff to the Protocol Registrar
and Pharmacy departments. She also maintains the Accrual Monitoring Program for slow-
accruing trials. She maintains the research Listserv to disseminate policies and current
information to DF/HCC clinical research staff. Other duties include office management, human
resources tasks, and budget assistance. She supervises the part-time File Clerk. The other
Administrative Coordinator works with the Assistant Director to administratively coordinate the
DSMC and DSMB. She also serves performs various other duties, including but not limited to
weekly timesheet preparation and office management as needed.
Clinical Investigational Data Analyst I/II (5.0 FTE)
The Data Analysts manage the Principal Investigator (PI)-initiated/In-house protocols from
multiple disease programs. They coordinate study team meetings for data collection methods and
CRF design, and monitor data for consistency and accuracy. Duties also include database
maintenance and setup, data computerization, and query generation and resolution. The Analysts
prepare data for statistical analysis, and generate reports for Clinical Research Coordinators
(CRCs) and PI’s. They work alongside the Biostatisticians and other members of the study teams
to ensure continuity and accuracy of clinical trials research data.
SAS Programmer (1.0 FTE)
The Programmer builds systematic procedural checks and programs to maintain, clean and
report data. She programs data retrievals in SAS for systematic reports – including writing
macros, automated patient accrual reports, and missing forms reports. She develops systems to
implement (and/or aid in the implementation of) statistical methodology for the analysis of micro-
array data. She develops security measures to maintain the integrity of the computerized
research database by working with the Biostatistical Science Database Administration (DBA)
staff. She monitors the operation of various systems and troubleshoots errors or system problems
as they occur. She documents procedures for maintenance and monitoring of computerized data.
She codes in SAS and SQL to produce reports for study teams, PIs, and other DFCI Departments
per data requests from Data Analysts and the Assistant Director. She also assists in piloting and
implementing new software tools and systems for DF/HCC.
File Clerk (0.25 FTE)
The File Clerk duties include filing and other projects as needed by QACT staff. He / she assists
the Administrative Coordinator with various administrative tasks.
Clinical Trials Audit Manager (2.0 FTE)
They conduct internal audits for DF/HCC clinical trials. Audits are performed on the processes
and documentation of clinical trial activities, which include team and individual audits, reviewing
data, preparing written audit reports, educating staff of regulatory requirements and
documentation of clinical trials and participating in quality improvement activities. The Auditors
maintain the Audit Policy Manual and QACT audit database. The Auditors schedule the audits
regularly, and prepare all report documents. Audit reports are presented to CLINPOC for review
and further action, as needed. The Auditors assist the QACT Director when preparing for
external audits, conducted by the Food and Drug Administration (FDA) and the National Cancer
Institute (NCI).
6
DFCI QACT
December 22, 2003
PATIENT ENROLLMENT IN CLINICAL TRIALS
Prospective Patient Registration by the QACT
Prior to the initiation of treatment, all protocol subjects are registered in the QACT Protocol
Registration System. The registration system is a computerized registry of all patients on DF/HCC
oncology protocols, and serves as a master list for various departments for summary statistics,
drug dispensing, NCI reporting and auditing.
This centralized registration process allows for the reporting of a variety of statistics. It also
allows for the monitoring of accrual rates, which is vital in determining whether a protocol will
meet the accrual objectives that are outlined in the protocol.
An investigator, treating physician, research nurse or CRC is responsible for registering a subject
with the QACT. Registration involves faxing a completed protocol specific eligibility checklist and
consent to the QACT.
The steps to register a patient as a new subject on a clinical trial are outlined below:
1.) Check the Clinical Systems Dictionary to assure that a new subject should be
registered to the protocol
Make sure the protocol is open to accrual
Read the comment section for special instructions
Check for randomizations or dose escalations (For dose escalation, see Procedures for
Phase I Studies)
2.) Verify Patient Eligibility Checklist
All of the eligibility requirements must be completed
The treatment must be starting on or after the date the registration materials were
received
All of the lab values must fall within the required ranges
Labs must be dated within 2 weeks (unless otherwise specified in the protocol document,
e.g., BMT protocol labs are within 42 days)
Double-check any “N/A”’. Is it a required answer or really N/A?
The registering person must sign and date the checklist
3.) Verify Consent Form
The consent form must be for the appropriate protocol
The consent form must be currently approved
The consent form must be signed and dated appropriately
For therapeutic protocols, an attending physician with a 1572 must have signed and
dated the consent
For ancillary protocols, a doctor or nurse must have signed and dated the consent form
If a CRA signed the consent form, they must be approved by the Principal Investigator to
obtain consent
Every page of the consent must be included
All questions in the consent form must be answered, if applicable (e.g., additional blood
samples)
7
DFCI QACT
December 22, 2003
4.) Register the Patient in the Clinical System
TO LOGIN TO THE CLINICAL SYSTEM FROM A PARTNERS TERMINAL
1.) Go to “start” menu
2.) Go to “Partners Applications”
3.) Select “DFCI Clinical Systems”
4.) Log in
TO REGISTER A PATIENT IN THE CLINICAL SYSTEM
1.) Enter into the system by entering your user name and password
2.) Enter “Clinical Applications”
3.) Enter “QACT/Protocol Research”
Look up the protocol in the Dictionary by going to “Dictionary” and entering the 5-digit
protocol number to check as outlined above that additional subject may be registered
4.) Num Lock out to get back to the menu
5.) Enter “SO” – Study Options
6.) Enter “UP” – Update/Display Status
7.) Enter patient’s medical record number or enter the first 3 letters of the patients first and last
name (e.g., for Mary Smith, enter SMI,MAR) If registering the patient to a Therapeutic
protocol, make sure he/she isn’t currently registered on another therapeutic study. If so, they
must be taken off the therapeutic protocol listed before registering them to a new one. In this
case, the registering person should be consulted.
8.) Enter “A” to add study to the patient file
10.) Enter protocol #
11.) Enter date registered
12.) Enter hospital name
13.) Enter primary MD
14.) Enter registering person
15.) Consent questions – If applicable, enter answers found on consent form
16.) Enter date received in QACT
17.) Enter disease program
18.) Enter disease subcategory
8
DFCI QACT
December 22, 2003
19.) Eligibility Code = “E” for eligible
20.) Consent received in QACT = “Y”
21.) Types of registration:
F = Fax *
A = After Hours *
R = Retrospective *
I = Interim (Compassionate Use)
T = Telephone
O = Other
* Most commonly used types of registrations
22.) Ok to file = “Y”
23.) Send confirmation forms = “Y”
24.) Take off study = “N”
TO REGISTER A NEW PATIENT IN IDX (This must be done if the patient is not already
assigned a DFCI medical record number before registering them to a protocol.)
1.) From the main menu in the Clinical System, choose “IDX Applications”
2.) Enter Choice = press Enter
3.) Enter Group = press 2
4.) Select Function = press 3
5.) Select Activity = press 103
6.) Enter Last Name, First name – enter first few letters of last and first name and compare to list
to avoid creating duplicate records
7.) Social Security Number (only if given)
8.) Type Date of Birth
9.) Sex
10.) Race
11.) Ethnicity
12.) Other Hospital #
13.) Street address (on line 1)
14.) City, State
15.) Zip Code
16.) Primary Clinic = QCCA (for adults) or QCCP (for pediatrics)
9
DFCI QACT
December 22, 2003
17.) Joint Venture (Type “?” to see choices):
Used for adult patients who will be treated at BWH
Or pediatric patients who will be treated at CH
18.) DFCI: type “G” to generate a 6-digit DFCI number
19.) F10 to save
20.) F7,Q to quit
21.) F7,Q to quit again
22.) F10 until you get to the main menu
PROCEDURES FOR PHASE I STUDIES
1.) Check Dose Escalation Report in the Dictionary
2.) On the Study Options menu, go to “Study Reports”
3.) Go to “Protocol Reports”
4.) Go to “Dose Escalating Study Report”
5.) Enter protocol #
6.) Print out report
7.) Verify that it is appropriate to register the patient to the dose level indicated. The Protocol
Dictionary will tell you how many patients should be enrolled on each dose level. You will
also find this information on the Dose Escalation Study Reports.
8.) Register the patient to protocol
9.) Dose level comment follows the wording on the Dose Escalation Report
INFORMATION TRANSFER FROM THE REGISTRATION SYSTEM
Information in the QACT Protocol Registration System is transferred in real time to the BWH
BICS computing system and CH Chemotherapy Order Entry (COE) for electronic chemotherapy
order-entry. If an MGH patient is registered, a manual link is also necessary to the Enterprise
Master Patient Index (EMPI) computing system. This manual link is the responsibility of the
Registrar. The benefit of linking these systems is to ensure patient safety by verifying that
patients are eligible and have consented to participation in a clinical trial or non-protocol
treatment.
Registration information is also transferred every night to the INGRES Research database. A
subject must be registered before data may be submitted to the database for them.
If a participant is not registered, the treating physician cannot order drugs. Likewise, if a
participant is not removed from protocol, the physician cannot order non-protocol therapy.
10
DFCI QACT
December 22, 2003
Retrospective Registrations
Retrospective registrations for therapeutic protocols are not allowed. An exception to this is some
minimal risk studies, where a high volume of participants is recruited daily registrations are
accepted retrospectively in batches by fax or mail. In these cases, the study team seeks approval
from the QACT Director. The Protocol Registrar will document in the QACT Clinical Research
System that approval has been granted by the QACT Director.
Development of Eligibility Checklists
When a research protocol is activated or amended, the QACT Registrar generates a new
document or revises an existing eligibility checklist from the protocol document, which is found on
the adult or pediatric online Oncology Protocol System (OncPro). For cooperative group studies
or industry-sponsored trials that may generate their own checklists, the QACT develops a “Front
Sheet” to capture additional information not found on the checklist, such as patient
demographics, lab values, test dates and randomization arms or dose levels for randomized or
phase I dose-escalation trials, respectively.
The Registrar notifies the OPRS online team that a checklist has been generated. In the case of
Front Sheets, the cooperative group or sponsor’s checklist is scanned online by the Office for the
Protection of Research Subjects (OPRS) Online Team.
In the event that an eligibility checklist is not required by the protocol, a QACT Registration
Form is put online to capture patient demographics for patient registration in the QACT. The
Protocol System Coordinator or Registrar comments in the QACT Clinical Research System that
a checklist is not required.
Eligibility Checking Process
Protocol-specific eligibility criteria are established to identify the target population and ensure
patient safety. When an investigator identifies a potential study candidate, he/she must confirm in
detail if the candidate is appropriate to participate in the study. The QACT eligibility checklist
assures that all inclusion/exclusion criteria are met prior to protocol enrollment.
The completed eligibility checklist is faxed to the QACT along with the signed entire consent
document. The QACT does not register a patient until all eligibility tests have been completed
and all values are made available to the QACT.
All tests that are required to determine eligibility must be completed within the time frame
specified in the protocol.
If a time frame is not specified in the protocol, tests must be completed as follows:
Lab tests required for eligibility must be completed within 14 days prior to study enrollment by
the QACT.
For protocols requiring measurable disease, baseline measurements must be completed
within 14 days prior to study enrollment by the QACT.
Examples: flow cytometry, HLA typing, fluid cytology, tumor markers and hormones
(CEA, CA-27-29, CA-125),
Non-lab tests required for eligibility must be performed 30 days prior to study entry.
Example: radiological scans
For bone marrow transplant (BMT) protocols and non-protocol treatment plans, eligibility tests
must be completed within 42 days prior to enrollment by the QACT. The extended period of
time is allowed to facilitate insurance approval while ensuring patient safety.
11
DFCI QACT
December 22, 2003
Consent Checking Process
Investigators have an obligation to obtain informed consent from a patient (or the appropriate
surrogate) before enrolling him/her as a subject on a clinical trial. (Please refer to DFCI IRB
Policies and Procedures for policies on this issue.) Written consent must be documented on the
valid DFCI IRB-approved consent, which can be found on adult or pediatric OncPro. Effective
January 2002, all pages of the consent must be faxed to the QACT along with the eligibility
checklist for patient registration, unless the protocol specifies differently. If that is the case, the
Protocol System Coordinator or Protocol Registrar enters an appropriate comment in the QACT
Clinical Research System. If a consent form has imbedded questions within it, all questions must
be answered for the form to be considered complete.
An expired or invalid consent form is not accepted by the QACT. If this happens, the Protocol
Registrar notifies the registering person and/or person who obtained consent that the patient
must be re-consented before s/he can be registered. Non-protocol treatment regimens do not
require the consent form to be IRB-approved.
All pages of the consent form must at minimum, bear the patient’s name and hospital number on
all pages.
Consent to a therapeutic trial must be obtained by an attending physician who has an active, NCI
1572 on file with the QACT. Otherwise, the signature page must be co-signed by an attending
with an active 1572 on file in the QACT. For non-invasive minimal risk protocols, Principal
Investigators can delegate the duty of obtaining consent by sending written notification to the
Protocol Registrar. The Protocol Registrar documents this in the Clinical Research System.
The signature of any staff member on the consent must indicate that s/he was involved in the
consenting process and that the participant was presented with a clear explanation of the protocol
and given the opportunity to ask questions.
RANDOMIZATION PROCESS
The Protocol Registrar is responsible for randomizing patients to treatment arms for some non-
industry-led and non-cooperative group trials. The Protocol System Coordinator is instructed by a
statistician in the Department of Biostatistics on how to perform the randomization. The Protocol
System Coordinator then documents the instructions in the QACT Clinical Research System,
which the Protocol Registrar will refer to. The Protocol Registrar documents the randomization
assignment in the QACT Clinical Research System, unless the protocol is blinded. If the protocol
is blinded, the Protocol Registrar conveys the randomization assignment to the appropriate
departments (e.g., Pharmacy) as directed by the randomization instructions.
PHASE I DOSE-ESCALATION TRIALS
The Protocol Registrar is responsible for monitoring all non-industry-led and non-cooperative
group Phase I trials. The dose escalation schema for the protocol is documented in the QACT
Clinical Research System by the Protocol System Coordinator, adding “DOSE-ESCALATION
(QACT)”, for the Protocol Registrar to refer to. Patient registration is denied if the specified
waiting period between and within cohorts has not been met. The DFCI Institutional Review
Board (IRB) must approve revisions to the protocol if additional patients, cohorts or dose-levels
are to be added. The Protocol Registrar assures that the dose-escalation schema is followed
exactly as it is written and appended in the protocol.
12
DFCI QACT
December 22, 2003
NON-PROTOCOL STANDARD TREATMENT REGISTRATION
Some subjects may be registered on a standard regimen not part of a clinical trial. The regimen
may be commercially available drugs or a specific procedure. The treatment is designated by a
3-digit number created by QACT.
DF/PCC NETWORK AFFILIATE REGISTRATION
For DF/PCC Network Affiliates, consent must be obtained on a current, valid consent form from
that hospital and the completed QACT-generated eligibility checklist must accompany the
consent.
The Protocol Registrar does not register a participant from a non-DF/HCC institution, unless that
hospital is named on the cover sheet of the protocol and the IRB from that hospital has approved
the protocol for use.
If a hospital must be added to the Provider Dictionary in the QACT Clinical Research System, a
request must be made to Nancy Crehan in the Access Management Department.
INDUSTRY-LED AND COOPERATIVE GROUP REGISTRATION
For industry-led and cooperative group trials, often registration must occur at the sponsor/
cooperative group level before registering with the QACT. Registration in the QACT must still
occur before treatment is administered. The QACT cannot register a patient from an outside
hospital on a sponsored trial unless the hospital’s name appears on the cover sheet of the
protocol and the IRB from the outside hospital has approved the protocol for use.
For patients enrolling in a CALGB study for treatment at a DF/HCC institution, the QACT-
generated Front Sheet (or checklist) must accompany the consent. For patients treated at a non-
DF/HCC institution, the CALGB checklist and confirmation of registration must accompany the
IRB-approved hospital consent.
NON-PATIENT VOLUNTEER REGISTRATION
DFCI Clinical Research Policy:
Purpose: The purpose of this policy is as follows:
a. to ensure safety for non-patient volunteers in clinical research
b. to formalize the process for including non-patient volunteers in protocols
c. to fulfill ethical, legal, and regulatory requirements
Scope: All non-patient volunteers in clinical research will be treated in the same way as
patient subjects. Record keeping and IRB approval is required.
Policies: Non-patient volunteers at DFCI have the right to follow the same procedures that
a patient volunteer would undergo when registered to a Clinical Trial.
Recruitment, medical records, consent forms, procedure forms will all be
followed.
Procedures:
1. Non-patient volunteers participating in research must be recruited according to a DFCI
IRB approved clinical protocol.
13
DFCI QACT
December 22, 2003
2. Non-patient volunteers undergoing invasive procedures or administration of
pharmacologically active substances must be registered as a DFCI volunteer, generating
a chart to be maintained in Medical Records. All appropriate material must be filed and
accessible in this chart. Blood draws are exempt. Bone marrow aspirates are not exempt.
3. Non-patient volunteers undergoing invasive procedure or administration
pharmacologically active substances will sign a consent form, will be registered with the
QACT and a copy of the consent form will be filed in the volunteer’s record. Blood draws
are exempt. Bone marrow aspirates are not exempt.
4. Non-patient volunteers undergoing invasive procedures, such as bone marrow biopsies,
will be managed as per standard patient care. Procedure forms, with all sections
completed, must be completed.
5. Individuals executing any invasive procedure on a non-patient volunteer must be
appropriately credentialed to perform that procedure.
6. While non-patient volunteers who are not undergoing invasive procedures or receiving
pharmacologically active substances are exempt from this policy, investigators must still
adhere to record-keeping requirements as specified in the IRB-approved protocol.
ELECTRONIC CONFIRMATION OF REGISTRATION
Effective November 2001, electronic confirmation of registration is automatically sent to the
registering person, Principal Investigator, treating physician and study contacts for protocol
patients. Hard copies are generated upon request.
When a name is not in the QACT Clinical Research System, a request to add it to the Provider
Dictionary must be sent to Patient Accounting. (Please see Provider Dictionary Update Form
attached.)
AFTER-HOURS REGISTRATION
Normal business hours for the QACT are 8:30 AM to 5:00 PM. Patients are enrolled and
randomized in clinical trials or non-protocol treatment during normal business hours, unless an
emergency arises where a patient must be treated before the next business day.
After hours registration involves calling the QACT main number (option 1) and leaving a detailed
description of the patient’s eligibility, leaving a call back number, and faxing the signed consent
form and completed eligibility checklist to the QACT. Registration occurs off-site after normal
business hours.
The QACT Registrars, Data Analysts and Assistant Director rotate weekend coverage on a
volunteer basis and are compensated for 10 hours at his/her current hourly rate. For weekday
after-hours coverage, they are compensated 8 hours at their current hourly rate. For holidays,
they are compensated 5 hours at their regular hourly rate.
THE ONCOLOGY PROTOCOL SYSTEM
Protocols, consent forms, eligibility checklists and priority lists are available on the online
Oncology Protocol System (OncPro). There are two versions of OncPro: adult and pediatric,
which are managed by the OPRS.
14
DFCI QACT
December 22, 2003
REMOVING A SUBJECT FROM PROTOCOL OR NON-PROTOCOL TREATMENT
When a subject will no longer be followed on protocol and no further data will be collected from
them, the QACT Registrar must be officially notified via telephone, fax, or e-mail. The study
number, the reason the participant is being taken off-study, the effective date, as well as the date
treatment ended if known, must be specified. The Protocol Registrar then removes the subject
from study by updating their record in the QACT Clinical Research System.
The categories for removing a participant from protocol or non-protocol treatment are as follows:
1. Cancelled (never began treatment)
2. Ineligible
3. Completed protocol requirements
4. Unacceptable toxicity
5. Progressive disease/relapsed
6. Withdrawal of consent
7. Died (specify date of death)
8. Lost to follow-up
9. Other (specify)_______________
10. Patient withdrawal of consent but agrees to be followed
Due to a chemotherapy-order entry safety mechanism that is built in to the QACT Clinical
Research System, a subject cannot be registered to more than one therapeutic trial at the same
time but can be enrolled in multiple minimal-risk, ancillary studies. If a subject is not removed
from a therapeutic protocol, the physician cannot order non-protocol therapy or register the
subject to a second therapeutic protocol. If the subject must be treated on a different therapeutic
study but the off-study date is unknown, in the Clinical Research System the Protocol Registrar
will enter one day prior to the registration date of the new study and will document the reason off
as “9: Other- switched to other protocol”.
If the date of death is not in the patient display banner in the patient record, it is advisable to send
that information to Health Information Services (HIS).
PROTOCOL CLOSURE NOTIFICATION
Effective March 2002, the Protocol Closure Form must be sent to both OPRS and QACT. The
QACT Protocol System Coordinator updates the Clinical Research System with this information.
When deemed appropriate by the QACT Director, protocol registration files are moved to an off-
site storage facility. If those records are needed, the QACT Director must be notified and a copy
of the documents will then be prepared for the requestor.
PROTOCOL COMPLETION/TERMINATION NOTIFICATION
In order to formally complete a study file, investigators must notify the IRB when a study is
terminated or completed or after data analysis is complete by submitting a final Continuing
Review Form. (Please refer to the DFCI IRB Policies and Procedures). The QACT receives
electronic notification from the OPRS, and the Protocol System Coordinator or Protocol Registrar
updates the QACT Clinical Research System.
15
DFCI QACT
December 22, 2003
REPORTS AVAILABLE FROM THE QACT
There are various reports available from the QACT relating to accrual statistics for research
protocols.The Protocol System Coordinator or Protocol Registrar must be contacted if a report is
needed.
QACT reports include the following:
Patient Accrual Report . This list can be generated for any protocol, and it contains a
summary of information about each patient registered on the protocol. The lists are
generally sorted chronologically by date entered, but they can also be sorted
alphabetically by patient name, or in terminal-digit order of hospital medical record
number.
Special Protocol Accrual Report. This report presents accrual by periods across
protocols or by specific categories such as disease sites, phase and sponsor.
Protocol Population Accrual Figures (Race, Gender, Ethnicity, and Service Area). This
type of report is useful for grant applications.
ACTIVE PROTOCOL ACCRUAL MONITORING
The Protocol System Coordinator monitors accrual on a weekly basis. If a study is within 10% of
total accrual, the Protocol Systems Coordinator notifies the Principal Investigator, and states that
the study should be closed once the accrual goal is met.
The Protocol Systems Coordinator reviews the accrual of cooperative group studies in which
DF/HCC is involved. Accrual may continue as long as the study remains open with the
cooperative group. Industry-led trials are monitored similarly; accrual is not halted on these
protocols if they are multi-center trials.
DATA COLLECTION
Cancer treatment is largely based on clinical research. Therefore, careful and accurate collection
of protocol and non-protocol data is essential to reliable answers to scientific questions posed in
research protocols.
The CRF is a data-gathering tool, and is developed by the QACT Data Analyst. CRF design
refers to the process of identifying what data must be gathered to meet study objectives. The
Data Analyst refers to the protocol document to identify information that must be collected for
computerization and data analysis. Not all required data that are specified in a protocol need to
be computerized in the research database/Ingres system. However, all required data must be
documented in a patient’s medical record.
During CRF design, the study team works together to agree on data to be collected to meet the
study objectives. The study team is comprised of individuals involved with managing the clinical
trials and may include: the Overall Principal Investigator (PI), Site PI, clinical research coordinator
or assistant (CRC/CRA), biostatistician, research nurses from all collaborating institutions and
QACT Data Analyst.
The Forms Design Process
CRFs are computerized by the QACT using Visio software. The data manager for patients
enrolled in a given protocol completes them. CRFs typically include the following:
On-Study form
Treatment form
16
DFCI QACT
December 22, 2003
Lab form
Summary form
Follow-up form
Other protocol-specific forms
Generally, the Data Analyst coordinates study team meetings to facilitate the forms development
process. The study team and Data Analyst work together to choose the specific data points they
would like to collect. The QACT Data Analyst drafts preliminary forms, referring to the protocol
document during the process. Pertinent sections include planned objectives, eligibility criteria,
treatment plan, expected toxicities, dose modifications, follow-up, measurement and response
assessment, and statistical considerations. The Data Analyst incorporates QACT standards and
coding conventions into each CRF. The study team is asked to review the preliminary draft forms.
During this review, the Data Analyst advises the study team to be critical of whether the forms
properly reflect the statistical and data collection needs of the protocol and whether data has
been neglected. Once all parties have approved the CRFs, the forms are finalized by the
Department of Biostatistics and published on the online Oncology Protocol System (OncPro).
Unless the protocol states differently, forms are due as shown in Table 1.
TABLE 1 - SAMPLE DUE DATES FOR PROTOCOL FORMS
ON-STUDY Within 2 weeks of subject registration
TREATMENT Every 3 months during treatment unless Phase I,
then after every cycle
SUMMARY Within 1 month of treatment completion
FOLLOW-UP At least every 6 months while protocol is open,
depending on the protocol
OTHER FORMS As specified in the protocol or on the forms
themselves
Study teams are encouraged to approve and finalize forms at the time of study activation for
prospective data collection. In particular, the PI and Statistician must approve the final draft of
CRFs. For in-house trials, the CRFs must be created early in the process. The Data Analyst
generally waits until three subjects have accrued to a study to have some data reflected on forms
before the forms are finalized and database tables are set-up by the Database Administrator. This
is to test the forms for appropriateness and accuracy. The forms process is complex and it can be
costly to make major changes to the database once it has been set up.
The QACT is not responsible for CRF design for all protocols. Some cooperative groups and
industry-sponsors provide CRFs for the CRC/CRA to complete and in this case, the group
computerizes the data. These forms differ in complexity and design from QACT-generated CRFs,
but serve the same purpose of summarizing a subject’s protocol treatment, including information
needed for analysis of the protocol as well as preparing an FDA submission for drug approval.
17
DFCI QACT
December 22, 2003
Data Collection onto CRFs
Data collection involves reviewing medical information that has been abstracted by a CRC/CRA
and transcribed onto CRFs, retrieving data from affiliate hospitals and gathering information from
various databases. Ultimately, the PI assumes the overall responsibility for data that are
collected. The QACT Data Analyst is assigned to a protocol to organize the data collection
process, to manage the computerized Ingres database, and to assure the quality of the data that
are being collected for statistical analysis and report writing.
The QACT performs quality assurance for most in-house protocols and is active in the data
collection process. All therapeutic DF/HCC protocols should be quality controlled by the QACT.
Cooperative group studies (CALGB, NSABP, RTOG, COG, GOG and others), most industry-
sponsored protocols, and any other protocols for which collected data are sent to a source other
than DF/HCC for analysis are not included in this process.
CRFs should be completed using permanent black ink to ensure a good copy, and CRCs must
submit the original to the QACT for computerization. Whiteout should not be used to correct
mistakes; instead, all errors must be marked with a single line drawn through the mistake, and be
noted with initials and date the correction was made. The CRC must keep a copy of the
completed CRFs for the research file.
The QACT expects the study team to meet regularly (at least 4 times per year) to review the
progress of the trial. Data should be submitted to the QACT according to the protocol schedule
or as instructed on the CRF and should be submitted to the QACT on an ongoing basis, rather
than in bulk. All CRFs are date-stamped upon receipt in the QACT.
COMPUTERIZATION OF DATA
After any problem areas have been clarified and the first three to five (3-5) patient forms are
received, the QACT Data Analyst creates a protocol database with help from the Database
Administrator (DBA) and Biostatistician to flag range errors. This process takes approximately
one week to complete.
Before data is computerized, the Data Analyst performs quality control measures on the CRFs
that are submitted to the QACT. For example, the Data Analyst reviews CRFs for legibility and
checks for data consistency, as well as improper use of values. Data cleaning programs can also
be executed to check for inconsistent data. Any discrepancies with the data are listed in a query
report to the CRC/CRA. All queries should be answered within one week.
Data Requests
Biostatisticians require ample time to conduct a thorough review of all the study endpoints and
issues. Last-minute requests for data analysis should be avoided. Data requests must be
made in writing to the QACT Assistant Director and have the approval of the PI. The Request
Form (please see Request Form attached) must be filled out completely to expedite the request.
A minimum of one (1) week for programming should be allowed for, depending on the request. If
the data requested has not been processed and keyed, allow two to four (2-4) weeks. All
requests require programming time and effort; therefore, careful consideration should be given to
request information in advance.
18
DFCI QACT
December 22, 2003
Incomplete Forms/ Missing Forms/ Queries
The QACT Data Analyst is responsible for generating missing forms reports on a regular basis to
monitor the data collection process. In addition, the Data Analyst can request missing information
or data in one of two ways:
1) Individual or patient-specific query
For individual forms with missing or questionable data, the Data Analyst will notify the
CRC/CRA electronically. A copy of the query and the reply is kept in the QACT, and the
database is corrected with the appropriate information once the response is received. To
document this process, the Data Analyst maintains an Excel spreadsheet consisting of
minimal information due to privacy reasons.
2) Formal data request
The QACT utilizes computer programs to notify the CRC/CRA of missing forms and/or
Missing information across all protocol patients on a given study. This allows the Data
Analyst to request information from the CRC/CRA if a specific CRF, survival or relapse
information is overdue.
If forms are queried, the Data Analyst performs corrections in the database. Statisticians analyze
all protocol data after the Data Analyst completes all updates in the database. The Statistician
will work with the Data Analyst to check all fields for missing data or inappropriate ranges,
account for all eligible patients, and close the database once analyses are complete.
DOCUMENTATION AND STORAGE OF DATA
Documentation Procedure
Each protocol computerized in the QACT has an associated binder, which includes a copy of the
protocol, important correspondence relating to the forms (excluding data queries that do not
pertain to the interpretation of the forms), SAS programs, coding conventions and the CRFs. The
binder may also include an updated protocol-patient accrual list.
Storage Procedure
Once the CRFs have been reviewed, submitted, and appended to the database, they are filed in
the QACT. The CRC should have maintained in their research file a copy of all CRFs submitted to
the QACT. CRFs are the written record documenting information that has been computerized.
Whenever computerized data looks questionable or more specific information is required, the
forms can be referenced as a backup.
All forms for a given protocol are stored on-site in the QACT while that protocol is active. Forms
collected for protocols that are inactive or for which data is not being analyzed are housed at an
off-site storage facility.
The Department of Biostatistics conducts nightly backups of all computer data in Ingres. Those
tapes are stored offsite. The QACT conducts nightly backups of all computer data, which is stored
in the QACT.
19
DFCI QACT
December 22, 2003
DATA MONITORING PROGRAM
A new process of data monitoring was proposed November 2001 to CLINPOC for PI-initiated
clinical trials, and has been implemented. This process quality assures data that are collected
from in-house studies. Data completion and database accuracy is reviewed, and this creates
opportunities for individual education/ training to CRCs/CRAs. Data Monitoring targets newly
opened protocols after the first three to five (3-5) patients have accrued to ensure that data are
being collected and managed appropriately. Currently, a Data Analyst III is performing the data
monitoring.
Objectives
To monitor on-going trials for quality assurance of case report forms designed by the QACT
and prospective data collection.
To review the status of data computerized in the research and registration databases.
To educate study team members on data collection methods and accurate reporting of study
data on CRFs.
To quality assure the data collection process for accuracy and efficiency.
To be in compliance with FDA guidelines (section 2.2.2 Study Monitoring) for good clinical
practice.
Methods
Protocol Selection -The QACT Data Monitor (allotted 50% of a position) will select one active in-
house protocol per month for monitoring. The protocol must have an active status from OPRS
with an updated continuing review (check REX system) . Also, the protocol should have less than
7 subjects accrued. The protocol representing one disease program, will be monitored at all local
sites participating in the trial. The overall PI will be notified of the monitoring date at least 4
weeks in advance along with the site PIs, CRA/CRCs, QACT Data Analyst and other supervisory
staff including the QACT Director, Nancy, and Glenn. Factors to be considered for selecting a
protocol are number of patients accrued, number of data queries, delinquent forms submission,
date of last internal audit for CRA/CRCs and upon request or recommendation from the Internal
Audit Manager based on major violations on data collection. Another factor to take into
consideration is a study that will be analyzed for national publication in a journal or meeting (e.g.
ASCO or ASH).
Patient selection – All of the patients or at least 2 patients per site will be randomly selected and
monitored by the QACT Data Monitor. The list of selected patients and a missing forms report will
be sent to the CRA to prepare the research files with the CRFs for all patients enrolled at the site
and order the medical record charts for the selected patients. If serious compliance issues are
found during the monitoring process, then the Data Monitor may request more patient records for
further review. This process should take no more than 2 days i.e. one day at each site.
Source documentation – All data reported on the CRFs should be verified in the source
documentation. However, only the selected patients will be reviewed with the medical records for
data accuracy on the CRFs. This includes the patient medical record chart, shadow folders for
CRFs, flow sheets initialed or signed by the treating physician or nurse.
Common problems to look for:
miscoding, transcription errors, illegible forms
incomplete or missing forms, blank values
eligibility checklist – verify patient eligibility
missing follow-ups – document reason
20
DFCI QACT
December 22, 2003
Database verification – A random selection of the forms submitted should be checked for
completeness and accuracy for data entry errors and other discrepancies in the QACT research
database. The Data Analyst assigned to the protocol will be informed of any findings and be
responsible for any necessary revisions or corrections. The procedural checks in the upd8
system will be reviewed including the key structure, correct attributes assigned in the tables, and
logical checks. Additional procedural checks may be recommended for the database integrity by
sending a request to the Database Administrator.
Queries and Corrections - The Data Monitor will query all discrepancies found during
monitoring. A detailed query summary report will be sent to the CRA/CRCs and Data Analyst
within one week of the final monitoring visit. Corrections to the original forms should be properly
documented by crossing out the original data item with one line of dark ink, writing the correction
on the right side, initial and date of change. It is helpful to write ‘Correction’ on the form and
highlighting the data item when submitting to the QACT. All queries should be resolved within 2
weeks after the detailed summary report is sent. The Data Analyst assigned to the protocol is
responsible for follow-up on all queries and any database corrections that are needed.
Missing forms report – The Data Monitor will retrieve data from the research database to
account for forms to be submitted and entered in the QACT. A copy of the report will be sent to
the study team within one week of the notification letter. Patient lists will be reviewed by
institution and forms will be verified that they are completed per protocol requirement schedule. A
form submission schedule should be developed with finalized QACT forms. A second missing
forms report will be run after the final data monitoring visit to ensure all outstanding forms have
been submitted. The Data Analyst assigned to the protocol will be responsible for follow-up on
missing forms.
Patient Registrations – The Data Monitor will check the patient registrations by printing a study
report from the registration system (VAX) and verify the patients listed in the study database. The
consent forms and eligibility checklists will be reviewed for completeness, dates, version
numbers, and signatures as well as the date of registration. For randomized studies, the
randomization procedures and documentation will be checked for accuracy and completeness. If
patients went off-study, reasons for going off-study should be clearly documented in the study
files and an off-study form sent to the QACT Registrar. The Data Monitor will report any
discrepancies noted to the QACT Registrar prior to the monitoring visit.
Monitoring Report – The Data Monitor will prepare a final report detailing the results of the
monitoring visit. The report should include the following information
# of missing forms before data monitoring visit (all forms & files should be up to date 1
month prior)
identify eligibility checklist and consent discrepancies found
# queries/discrepancies between CRFs and medical records
# queries/discrepancies between CRFs and database
identify inconsistent data across sites on the same form
identify data items or forms that are filled out inconsistently
suggest data items or forms to be clarified or changed on the CRF
make recommendations for improving data collection methods to increase accuracy and
efficiency
report database verification reults
follow-up by the QACT data analyst, education coordinator, or internal auditor
The report will be sent to the Overall PI and study team CRA/CRCs, Data Analyst and QACT
Director. If multiple protocol compliance or data collection issues are cited, the QACT Director
may forward to ClinPOC for further review and action.
21
DFCI QACT
December 22, 2003
Follow-Up – The Data Monitor nay set up a follow-up meeting with the study team and Data
Analyst when necessary to review the report and recommend corrective measures. A follow-up
timeline should be determined between the Data Analyst and CRA/CRCs for corrective actions
and evaluation. For example- establish a monthly data management meeting for the disease
program or study team; schedule a 3-month follow-up visit, or monthly missing forms report.
ClinPOC Review – The Data Monitoring Summary Reports will be reviewed by ClinPOC every
six months.
CLINPOC
Overview
The Clinical Investigations Policy Advisory Committee (CLINPAC) was organized in 1986 to
advise on policies relating to the conduct of clinical trials and the two departments that manage
the clinical trials system at DFCI- OPRS and QACT. CLINPAC was reorganized in August 1994
and renamed the Clinical Investigations Policy and Oversight Committee (CLINPOC). The
inclusion of oversight as part of the title reflects the added authority given to the committee to
take corrective action when required (including enforcement of policies and procedures). In
September 1997, CLINPOC was once again reorganized to include representation from
institutions across DF/PCC in order to allow for their participation and involvement in the
oversight process. In July 1999, additional members were included to represent DF/HCC.
CLINPOC is peer-reviewed and is a part of a continuous quality improvement mechanism. As of
October, 2003, CLINPOC is reviewing its structure and is currently revising its policies and
procedures.
CLINPOC is responsible for the following:
1. Oversight of the DF/HCC clinical trials process
2. Development of policies to ensure high quality clinical research
3. Oversight of the two administrative offices involved in clinical research: the Office for the
Protection of Research Subjects (OPRS) and the Quality Assurance Office for Clinical Trials
(QACT)
4. Oversight of the Internal Auditing System
5. Oversight of the following clinical trial systems:
Protocol accrual monitoring program
Protocol Registration System
Computerization of clinical trials data
Quality control of clinical trials data
Protocol review
Affiliate participation in protocols
Data management systems for clinical trials
CLINPOC must communicate with the investigators to resolve issues noted in the oversight
process. Ultimately, CLINPOC has the authority to enforce the policy standards it develops.
Membership
CLINPOC meets on the first Thursday of each month. The QACT coordinates this meeting. The
following list provides position title only:
Chair, Adult Oncology
Co-Chair, Director, Biostatistics
DF/PCC Chief Medical Officer
DF/PCC Vice President for Clinical Program Development
Director, Clinical Trials Support
Chair, Pediatric Scientific Review Committee (PSRC)
22
DFCI QACT
December 22, 2003
Director, Cancer Epidemiology and Control
Clinical Director, Pediatrics
Co-Chief, Hematology Oncology
Director, Center for Hematology Oncology
Chief, Hematology/Oncology Division BIDMC
Co-Director, Sarcoma Clinic/Surgical Oncology
Associate Chief, Department of Radiation Oncology
Chair, Institutional Review Board (IRB)
Chair, Quality of Life (QOL) Committee
Chief Operations Officer
Director, Nursing Education and Clinical Practice
Director, Pediatric Oncology Nursing
Administrative support (ex-officio members) include:
Vice-President for Research
Director, Pharmacy
Director, OPRS
Director, QACT
Director, Risk Management
Audit Manager (3)
Meeting Coordinator
ACCRUAL MONITORING PROGRAM
The purpose of the Accrual Monitoring Program is to aid in the prioritization and monitoring of
protocols. The report identifies slow accruing protocols in order for a determination to be made to
increase accrual or close the trial to further accrual.
The QACT generates a report at least once a year listing slow accruing trials that are currently
open within each disease program. Phase I dose-escalating trials and cooperative, multi-center
group trials are not included in the report. The report is distributed to Disease Program Leaders
and Disease Program Scientific Review Committee (SRC) Representatives. For pediatric trials,
the report is forwarded to the Pediatric Clinical Director.
Trials are sorted by therapeutic and ancillary categories. The report includes: protocol number,
protocol name, study chair, phase, type of study (therapeutic or ancillary), activation date,
expected accrual, expected duration, accrual rate, actual accrual, accrual percentage, slow
accrual, reached 80% of expected accrual and time needed in years to complete the protocol.
The Chair of CLINPOC will compose a letter that will be sent to the Disease Program Leaders,
the Disease Program Scientific Review Representatives and the Pediatric Clinical Director
requesting a response to the report by a specified deadline. The Accrual Monitoring Program
“key” and a list of protocols specific to each disease program are maintained by the
Administrative Coordinator of the QACT.
The Disease Program Leader and Pediatric Clinical Director are responsible for contacting the
Principal Investigator to coordinate a response to CLINPOC. If the trial is to remain open, a letter
of justification and a plan for increasing accrual must be sent to CLINPOC. A subcommittee of
CLINPOC then reviews all written responses. The subcommittee consists of the Chair of
CLINPOC, Co-Chair or designee from Biostatistics, Director of Clinical Trials Support, Director of
the QACT and CLINPOC Coordinator to document the minutes of the meeting.
Upon review of the responses, the subcommittee which represents CLINPOC decides whether
the trial should remain open, be closed, be re-evaluated at a later time point, or whether further
23
DFCI QACT
December 22, 2003
information is required in order to make a decision. The Disease Program Leader, Pediatric
Clinical Director and Principal Investigator are notified in writing of any decision made by
CLINPOC.
Disease Program Leaders, Pediatric Clinical Director and Principal Investigators have the right to
appeal any decision made by CLINPOC.
INTERNAL AUDITING
DF/HCC’s internal auditing system oversees the compliance of the clinical trial process in data
collection and procedures. The purpose of the DF/HCC audit system is to assure a high standard
of quality for DF/HCC protocols by systematically evaluating the following areas of therapeutic
protocols:
1. Protocol compliance
2. Data accuracy
3. Protection of human subjects
4. Investigational drug handling
All active DF/HCC protocols are eligible for audits, including all NCI, pharmaceutical, and other
sponsored protocols. A protocol is eligible for audit once it has accrued five (5) patients. The
QACT coordinates all internal audits.
The Clinical Trials Audit Manager uses the protocol document as the basis for judging protocol
compliance. The specific areas are:
Informed consent
Registration and Randomization
Patient Eligibility
Pre-Therapy Requirements
Treatment Administration
Protocol Parameters/ Tests
Response evaluations
Toxicities
Data Collection
Investigational Drug Handling
CLINPOC reviews audit findings and approves or disapproves of the evaluation. The Overall
Principal Investigator (PI) is requested by way of a written audit report to correct any deficiencies
that the Clinical Trials Audit Manager identified. Three (3) months following the date of the audit,
the Clinical Trials Audit Manager may request written verification to ensure that the initial request
was completed. CLINPOC will review responses from the PI. Documentation of any changes is
maintained in the QACT audit files.
No protocol will be audited more than once in its lifetime unless CLINPOC recommends a re-
audit. DF/HCC protocols that are conducted at affiliate hospitals are selected for audit using the
same criteria as in-house protocols. Moreover, two or more protocols may be audited on the
same day at the affiliate hospital.
The Clinical Trials Audit Manager selects a protocol from all studies that are eligible to be audited
and attempts to distribute the audits evenly among the various DF/HCC disease programs. The
Clinical Trial Audit Manager performs audits of specific protocols upon request.
The QACT provides a resource document entitled, the Clinical Trials Audit Manual. The
Manual describes the auditing process in detail. All clinical researchers and data management
staff are advised to become familiar with the importance of and the procedures for audits.
24
DFCI QACT
December 22, 2003
Educational seminars are occasionally arranged to familiarize staff with the audit process and
assist them in preparing for an audit.
DF/HCC PHASE III DATA AND SAFETY MONITORING BOARD (DSMB)
The DSMB for Phase III clinical trials was formed in accordance with NIH requirements. The
purpose is to monitor study progress and potential risks to patients enrolled in protocols that are
developed by DF/HCC investigators. Board members include clinicians and biostatisticians from
across DF/HCC, as well institutions outside of DF/HCC. The DSMB meets semi-annually, and
reports findings to CLINPOC and the IRB. The first Institutional DSMB convened in March 2002.
PHASE I AND II DATA AND SAFETY MONITORING COMMITTEE (DSMC)
The purpose of the DSMC is to provide ongoing monitoring for high-risk clinical trials initiated and
conducted by DF/HCC investigators to ensure the safety of study participants as well as evaluate
the ongoing status of the trial. Membership is appointed by the Senior VP for Research and
includes:
Voting Members:
3 Medical Oncologists
1 ad hoc Physician as needed (Radiation Oncologist, Surgeon)
1 Biostatistician
1 Nurse
1 Pharmacist
(Chair will be one of the physicians)
Non-voting member:
1 Coordinator for meetings
The QACT serves as administrative support to the committee. Information that is to be provided
to the committee includes: current patient accrual, all adverse events that have been reported,
any response information that is available and a summary provided by the study team. Other
information (e.g. scans, laboratory values, patient charts) is provided as requested by the
committee. Minutes are kept and recommendations are made to the study teams and reported to
the IRB and CLINPOC. All trial and patient information must remain confidential. All DMC
members will sign a Confidentiality and a Conflict of Interest (COI) Statement related to the trials
being discussed. Members will recuse themselves from the discussion and voting if a conflict
exists for a given protocol.
Protocols that require monitoring are high risk DF/HCC-initiated protocols. They are identified by
the Study Team, Scientific Review Committees (SRC and PSRC), IRB and/or CLINPOC. High-
risk protocols may include, but are not limited to the following: gene transfer studies, vaccine trials
using live or attenuated viruses, new therapies being tested for the first time in humans, trials
initiated within DF/HCC but being conducted at multiple centers outside of DF/HCC, or studies
that are exceptionally complicated or intensive. Most high-risk sponsored trials initiated outside of
DF/HCC have their own monitoring committee. If these trials do not have a DSMC and if the
DF/HCC review committees determines that an increased level of monitoring is required, then
they will also be reviewed by this committee.
INDEPENDENT RESPONSE REVIEW
The purpose of this review process is to provide ongoing monitoring of the reported responses to
protocols that are DF/HCC-initiated or NCI-sponsored. This monitoring ensures that the reported
responses to a protocol are accurate. Three physicians have agreed to review all information
25
DFCI QACT
December 22, 2003
required to assess response. The QACT reports their findings to CLINPOC on a regular basis.
Partial or Complete Responses are reviewed, depending on the definitions of response in the
protocol. The QACT tracks all reported responses and conducts a review semi-annually. Studies
that have a large number of responses require a subset for review. The source data is reviewed
by the Auditors. A physician reviews films, scans or other information that need interpretation. If
there are discrepancies in the declared response and the findings of the independent response
review, the PI is given an opportunity to review and comment on the discrepancies. If the PI
disagrees with the review then an appeals process is initiated with a Subcommittee of CLINPOC.
HIPAA RESEARCH SUBCOMMITTEE
The HIPAA Research Subcommittee was formed in June, 2002 by the QACT Director. The
purpose of the subcommittee was to develop and implement strategies for DF/HCC as it faced
the challenges of the HIPAA regulation and confidentiality of research data. DF/HCC is committed
to the highest quality clinical research and maintaining the privacy of all patients who participate
in our clinical trials. This is a commitment that continues to evolve as new regulations address the
growth of technology associated with research.
With support from many sources, DF/HCC research programs develop different therapies for the
treatment of cancer. For example, DF/HCC activates 10 new cancer trials each month on
average and now has approximately 350 active therapeutic clinical trials under way. Currently,
more than 2,100 patients a year are enrolled in clinical research trials at DF/HCC. With the high
volume of research that is performed, the data that is collected includes protected health
information for each subject on every trial. The confidentiality of this enormous amount of
information is extremely important to DF/HCC.
The date for compliance with new HIPAA regulations was April 14, 2003. This subcommittee
worked to address all confidentiality and privacy issues of HIPAA within all areas of research, and
assure the protection of all private information that allows DF/HCC to move forward in the fight
against cancer.
The subcommittee is composed of the following members:
Director, QACT
Assistant Director, QACT
Director, OPRS
General Counsel Representative
Meeting Coordinator
NCI INVESTIGATOR 1572 RENEWAL
Upon the directive of the NCI, DF/HCC has implemented centralized process for obtaining and
updating NCI Investigator Status. The process includes the annual completion of a 1572 form
accompanied with a current Curriculum Vita (CV). Effective May 2002, the NCI also requires the
completion of a Supplemental Investigator Data Form (IDF) and Financial Disclosure Form (FDF).
(A-14) The QACT Administrative Coordinator works with the NCI Pharmaceutical Management
Branch to update all DF/HCC Investigators every year to meet the August 1st deadline in
Washington.
NCI Investigator Numbers are crucial for any physician who prescribes IND chemotherapy, as
well as those who will or potentially could have to co-sign an order or consent form. It is also
necessary for those who work with the NCI on grants or research.
The Administrative Coordinator coordinates the renewal process, commencing in June every
year. Investigators are advised to return all completed documents to the Administrative
26
DFCI QACT
December 22, 2003
Coordinator who will confirm that all required fields are completed and all signatures are obtained.
The Administrative Coordinator then forwards all documents to the NCI prior to the NCI deadline.
NCI does not register fellows, dentists, pathologists and psychiatrists. NCI does register
surgeons, radiation oncologists and other oncologists.
Staff Updates
The Administrative Coordinator works with the Risk Management Department at DFCI and staff at
the MGH Cancer Center on a monthly basis to be apprised of physician new hires, terminations
and changes in status (e.g., from Fellow to Attending-level). Based on this information the
Administrative Coordinator notifies new hires and new Attendings to register with the NCI through
the QACT.
The Administrative Coordinator also provides an updated listing of active NCI 1572 Investigators
to the QACT Protocol Registrar and Pharmacy Departments at DFCI and MGH. The Protocol
Registrar utilizes the listing during Consent Checking. Pharmacy assumes that if the Protocol
Registrar registers a patient to a therapeutic trial, then the consenting physician is an active 1572
Investigator on file with the QACT and the NCI. Pharmacy refers to the monthly update or
contacts the QACT Director or Administrative Coordinator if a question arises.
Research Listserv
The Research Listserv was formerly known as, Clinical Trials Information List Serve. Effective
December 11, 2001 it was renamed the Research Listserv to include some of the research
laboratories. (A-15) The Administrative Coordinator will make additions or deletions to the
listserv, based on the monthly updates, for electronic dissemination of information to active
DF/HCC clinical research staff. In addition, the Administrative Coordinator should be notified by
study teams if a new clinical research staff member (e.g., CRCs and research nurses) is hired or
resigns, so that the listserv will be updated to reflect the change.
CHANGES AND MODIFICATIONS OF POLICIES AND PROCEDURES
Occasionally, these Policies and Procedures may be revised as may be necessary or appropriate
to ensure fulfillment of institutional responsibilities under existing Assurances, to improve
operational efficiency or to address other concerns that may arise. All revisions will be
documented as an addendum until such time as a revised version of this document is prepared.
(Refer to DFCI IRB Policies and Procedures, dated July 18, 2002)
27
