1
Q
Conmed
A
Any medicine that patient is taking that is not the study drug
2
Q
Clinical research associate
A
Also known as a clinical monitor, trial monitor, or site manager
3
Q
INDA
A
Investigational new drug application: Application filed with the FDA after completion of pre-clinical and prior to human testing
4
Q
NDA
A
New drug application: submitted after completion of phase 1, 2, & 3 studies of clinical trials. Application filed with the FDA for sale and marketing of the drug product
5
Q
Phase 1
A
-usually healthy subjects (except oncology/HIV)
-Done to determine whether humans and animals shows significantly different responses to the drug and establish safe clinical dosage right
-Many predictable toxicities are detected in this phase
-use dose escalation (3+3 design)
-non blind
6
Q
Phase II
A
-studied in subjects w target disease
-single blind or double blind
-phase IIA: dosing requirements (how much drug should be given
-phase IIB: study efficacy (how well drug works)
7
Q
Phase III
A
-much larger sample size
-Double blind and crossover techniques are frequently used
-Difficult to design and execute it are usually expensive because of large number of subjects
-certain toxic effects, especially those caused by immunological processes, may first come apparent here
8
Q
Phase IV
A
-aka: Post marketing surveillance trial
-careful and complete reporting of toxicity by physicians after marketing begins
-monitoring the safety of a a new drug under actual conditions of use in large #s of patients
9
Q
PQV
A
-pre-qualification visit aka pre-site selection visit, qualification site visit
-conducted in order to confirm whether the site is qualified to participate in a study
-1 qualification visit per site per study
-MUST obtain a confidential disclosure agreement prior to PQV
-try to collect all essential documents
-can be waived if a PQV has been conducted by another CRA within the same year
-assess site facility: recruitment,budget,IP storage et
10
Q
SIV
A
Site initiation visit
-Conducted once this site has been selected and the site receives a greenlight approval
-IRB approval and all essential documents collected (CVs, FDs, MLs, GCP certificate, CLIA,CAP,RR) try to collect these at PQV
-only one SIV per site per study
-formal training provided by the CRA to personnel at site
-drug accountability
11
Q
RMV
A
Routine Monitoring Visit aka interm monitoring visit
-1st RMV is usually conducted 2 weeks after 1st subject has been enrolled/randomized
-multiple RMVs per site
-conducted in order to make sure site is following study specifications/guidelines
-drug accountability -regulatory binder maintained
12
Q
RMV prioritizing
A
1) sign in
2) review subjects who’ve had SAE
3) review newly enrolled subjects
4) review previously enrolled subjects
5) complete drug accountability
6) review regulatory binder
7) meet with PI and study team
8) schedule next visit
13
Q
COV
A
Close out visit aka termination visit
-occurs once per site per study
-conducted at the end of the study
-study close out letter is obtained from IRB
14
Q
CDA
A
Confidential disclosure agreement
-Legal contract between the CRO/sponsor and the site The outline confidential material, knowledge, or information that parties wish to share with one another for certain but wish to restrict access to or by third-party. It is contracted through which the parties agree not to disclose information covered
15
Q
ICH
A
International Council for harmonization
-A project that brings together the regulatory authorities of Europe, Japan, and the US and experts from some pharmaceutical industry and three regions to discuss scientific and technical aspects of pharmaceutical production
16
Q
SC
A
Study coordinator
-The CRA’s primary contact at the site
-Performed many tasks such as entering data, reporting Sae, ordering study drug, scheduling subject visit, scheduling monitoring visit, updating the site regulatory binder
17
Q
RC
A
Regulatory coordinator
-Person at the site that is responsible for maintaining the regulatory binder. They ensure all essential documents are kept up-to-date including CVs ML etc
18
Q
CV
A
Curricula Vitae
A resume that states the individual skills and background
19
Q
FDF
A
Financial disclosure form
-A document that confirms the PI or sub-I does not have any financial interest within the study
-Collected at the beginning and at the end of study
20
Q
SOA/1572
A
Statement of agreement
-Confirms that the PI is responsible for the overall concept of the study
-includes address of PI and sites where subjects are seen
-federal document
-Usually amended as trial goes on
21
Q
IB
A
Investigational Brochure
-a comprehensive document summarizing the body of information about an investigational product
-Atlas information regarding the safety of the drug and statistical data around adverse events associated with the drug
22
Q
CLIA
A
Clinical laboratory improvement amendments
-A laboratory certificate that certifies the lab
-Expires yearly an updated copy needs to be collected once expires
23
Q
CAP
A
Certified authorization professional
-An additional certificate that some sites have in addition to the CLIA
- It’s an objective measure of the knowledge, skills, and abilities required for personnel involved in the process of authorizing and maintaining information system
24
Q
RR
A
Reference ranges
-A range of numbers in which value is placed to determine if a result is normal
25
SSDL/DOA
Site signature delegation log/delegation of authority
-A log that has everyone at the site listed along with the tasks that they will perform that was delegated by the PI
-Make sure that those who are specifically delegated to do the task has been trained and suitable for the task
26
SOP
Standard operation procedure
-Step by step instructions compiled by an organization to help workers carry out Routine operations
-Used to aim to achieve efficiency, quality output, and uniformity of performance while reducing miscommunication and failure to comply with the industry regulations
27
CMP
Clinical monitoring plan
-The plan establishes the guidelines for conducting monitoring visits and related task for monitoring
-What they want you to do while you’re on site (ie. how much time spent at each site
28
NTF
Note to file
-A document that provides a detailed description regarding a discrepancy noted during the clinical study
-ie. there’s a confirmation letter missing so you make note of it to cover yourself, or temperature excursion
-NTF are general but should be in regulatory binder and eTMF
29
SDV
Source data verification
-A review of the data collected from the site to confirm that the data matches exactly what is entered in the EDC system
-SDV conducted to ensure the data collected is reliable
-SDV is process to evaluate the conformity of the data presented in CRF (case report form=the data collected in the EDC are CRF)
30
EDC
Electronic data capture
-Framework of the subjects chart
-Should be an exact replica of SDV
-only the site can enter data
-CRA will have read only access
-Only able to question the data or close the query
31
CRF
Case report form
-The data collected in the EDC are CRF
32
CTCAE
Common terminology criteria for adverse events
-only graded by PI
-from 1-5 (5 being death)
33
DBL
Database lock
-A lock of the data entered within the EDC system
-No changes or queries can be entered if the DBL occurs
-This typically occurs at the end of the study and is permanent
34
IA
Interim analysis/soft lock
-A lock of the data entered within the EDC system during setpoints of the study
-Typically this occurs when certain end points are reached
-This is not a permanent lock
35
IP
Investigational product (drug)
-The actual study drug that is used during a clinical study
36
SAE
Serious adverse event
-Any untoward event that may or may not be related to the study drug which results in death, hospitalization for 24 hours or greater, causes birth defect, causes significant disability, life-threatening, medically significant
37
AE
Adverse Event- Any untoward event that may or may not be related to the study drug that was not originally identified within the subject medical history
38
PD
Protocol Deviation
-An alter in the protocol guidelines that do not affect the subject safety
-if major deviation address with the PI and SC
-possibly retrain site
-enter NTF
39
PV
Protocol violation
-an altar within the protocol guidelines that affects the subject safety
40
SOC
Standard of care
-The normal care that is provided for the sites guidelines
41
TA
Therapeutic area
-Refers to a generalized organ system/disease in which a study is conducted
Ie. Oncology, cardiology, general medicine
42
Indication
-Specifics of the therapeutic area
-for example oncology is the therapeutic area and the indication would be prostate cancer, breast cancer
43
Regulatory Binder
Aka study file notebook, investigator site file, investigator site manual
-houses all regulatory docs
-essential documents collected and routed to sponsor
-reviewed and reconciled/replica of eTMF(CRO access)
-Delegation of Authority Log reviewed and verified
-gaps or delays noted in reporting expedited SUSARDS
-eTMF is a replica of this
44
CRF
Case Report Form
Used by sponsor to collect data from each participating subject
45
Informed Consent Document
-describe study in language the person can understand
-must be signed and dated by:
—subject or Legally Authorized Representative LAR)
—investigator
—person obtaining the consent (if not an investigator)
-subject must be given a copy
-Informed consent process is finished when study is closed and final reports are issued
-MUST make sure subject signs ICF prior to any study procedure being conducted
-subject should be re-consented if language has been changed in original ICF
46
eTMF
Electronic trial master file
-exact replica of regulatory binder (aka ISF)
-sponsor and CRA access only
47
Certified Copy
-copy of any source and it is stamped and signed by someone on site (usually the PI)
-certified copies of the EMR
-these are copies of the records that are printed and filed in the patients chart
48
Risk base monitoring
-Process of ensuring the quality of clinical trials by identifying, assessing, monitoring, and medicating the rest that could affect the quality or safety of a study
-study team decides they only want specific risk points (ie: informed consent, visit dates, inclusion/exclusion criteria met, dosing)
49
ALCOA
Attributable, Legible, Contemporaneous (sequential), Original, Accurate and Complete
-the guidelines/standards set by the FDA for data collection
50
IM
Investigator Meeting
-A meeting in which PI’s, SC‘s, medical team, study team, and sponsor team are present to provide formal training together with our site that will participate on the study
51
CRO
Clinical Research Organization
-Support for the pharmaceuticals, bio technology, and medical device industry in the forms of research services outsourced on a contract basis
-a CRO is contracted by a sponsor (ie. Johnson&Johnson) to conduct clinical trial
-the sponsor is the actual pharmaceutical or biotechnology company who makes the drug or device
52
Confirmation Letter
-Sent to the site via email prior to the site visit
-copy should be in regulatory binder
-need this for EACH visit. Usually want at least 7 days in advance
53
Follow up Letter
-all visits require this to be sent to the site via email after the completion of the visit
-all visits require this. Includes what you did during the visit, and findings or issues that need to be resolved
54
Share point
-this is where everything is housed
-each study has its own share point
55
Trip Report
-completed and finalized within 10 days of the visit (you will have 5 days from the last day of the visit to submit your draft and a remaining 5 days to finalize the TR
-a TR is completed after each visit regardless if the visit was phone or onsite
-often time the TR is returned by reviewer for revisions and updates
-The only approved TRs that are sent back to the site to be filed in the state regulatory binder is the SIV and COV
56
Drug accountability
-A recording keeping associated with storage, inventory, dispensation, and destruction of the investigational product (IP) used in clinical trials
-performed at SIV if the drug is onsite and also at RMV and COV
57
Temp tale
-rides with drug to site to make sure temp has not changed (temp excursion) and is accurate
58
How is drug accountability completed?
-Sites are provided with sponsor specifics temperature laws which they can wave to use their own site specific temp logs
-log is completed daily and the data for each day is recorded on monthly log
-review destruction log
59
Pharmacy Manual
-How the drug is to be administered
-How the drug is to be prepared
-How the drug is to be stored
-it details any supplemental tubing that is required
-This is the sites Bible regarding the drug itself
60
Temperature Excursion
-A temperature excursion is a spike or drop in the temperature of the storage location, as the CRA you are the first point of contact if this occurs
-The site should enter a note to file NTF to indicate what occurred
-If this happens the site should be instructed to quarantine the drug (remove drug until further instruction) and the drug should still be stored at the appropriate temperature
-as the CRA you should escalate to the study team and wait for instruction (destruction, return to inventory, send back to sponsor)
61
EDC
computerized system designed for collection of clinical data in electronic format (replaced traditional paper based system)
62
how do you use EDC as a CRA
match the information that is in the subjects chart (source) to what is entered in the EDC system. if data doesnt match you'll raise a query
63
Query
-should be discussed w site staff while on site
-Data Management Team and CRA can enter queries
-run data reports through EDC system
64
EDC system examples
-iMedidata/RAVE
-OC-RDC: Oracle
-DataLabs
-INFORM
-BioClinica
-eCaseLinks
65
CTMS
Clinical Trial Management System- software system used to manage clinical trials in clinical research
-only the clinical team and sponsor have access
-no site access. Always enter dates of visits in CTMS once scheduled
IE) Siebel, iMedidata, IMPACT
66
What do you use CTMS for?
-complete trip report
-enter protocol deviations
-track site issues
-enter site correspondence
-schedule planned visits
-provides site information for all sites participating on clinical studies
67
CTMS examples
-IMPACT
-IMPACT HARMONY
-i-Medidata
-Siebel
-CTMS
68
TMF
Trial Master File - system that houses all regulatory documents
-CRA conducts TMF reconciliation - making sure TMF matches Regulatory Binder
-make sure documents in TMF are not expired
69
TMF examples
-Veeva Vault
-eTMF
-pTMF
70
IVRS
Integrated Voice/Web Response System - system used to register, order, ship, and confirm the study drug
-perform subject screening and visits
-subjects are randomized here
71
IVRS/IWRS examples
-ALMAC
-IcoPhone
-ClinPhone
-Perceptive
iView
72
Causal Relationship
-there is a reasonable possibility that the event may have been caused by the drug
73
ADR
Adverse Drug Reaction - all untoward and unintended responses to an investigational medicinal product
-all AE (adverse events) judged to have a "reasonable" causal relationship to a medicinal product qualify as ADR
-"reasonable" there is evidence or argument to suggest a causal relationship
74
Unexpected Adverse event
an adverse event, the nature or severity of which is not consistent with the applicable product information
75
SUSAR
Suspected Unexpected Serious Adverse Reaction - serious and related to study drug and unexpected
-Reportable to: regulatory authorities, EC, IRB, Investigators
-notified w/i 7 calendar days of initial receipt if fatal or life threatening SUSAR
-notified w/i 15 calendar days of initial receipt if other serious SUSAR
76
SAE reporting procedures
-ensure the investigator follows the correct reporting procedures
-ensures SAE reported appropriately
-perform SDV of CRF and the SAE reporting form
-verifies SUSAR has been filed with the IRB
77
Reporting SAE
-notify all SAE to safety team w/i 24 hours
-notify IRB, EC (ethics committee)
-legal obligation according to ICH E6, SOA or Form FDA 1572
78
Database Reconciliation
Two AE databases
-CRF database (via data manager)
-SAE database (via drug safety)
What needs reconciling
-terminology
-dates
-causality/seriousness/etc
79
Half lives
How long the drug travels in the blood
80
MTD
Max tolerated dose
81
CSSRS
Columbia suicidal severity rating scale - used to assess a participant before being enrolled into a CNS study
82
HDRS
Hamilton Depression Rating Scale - used to assess a participant before being enrolled into CNS study
83
RECIST
Response Evaluation Criteria In Solid Tumors - the measurement tool tracker -used to determine the tumors response to the treatment
4 responses that are used to measure the outcome from the Nadir:
Progressive disease (PD) 20% increase
Partial Response (PR) 30% decrease
Stable Disease (SD), and
Complete Response (CR)
Non changing (NC)
Not evaluable (NE)
Longest Diameter (LD)
84
Common AE for oncology
Low hemoglobin.
Low ANC (absolute neutrophil count).
Diarrhea, vomiting, low WBC count, trouble breathing, painful urination.
Febrile neutropenia.
Pain
85
ANC
Absolute neutrophil count/neutropenia- less than 1500 cells per microliter
The absolute neutrophil count (ANC) is an estimate of the body's ability to fight infections, especially bacterial infections. These test results are often referred to as a patient's “counts.” An ANC measures the number of neutrophils in the blood. Neutrophils are a type of white blood cell that kills bacteria.
86
Febrile neutropenia
High fever with low ANC count
87
Solid tumor
Abnormal mass or cyst that do not contain liquid(blood) areas. It could be malignant or benign. Solid tumors are sarcomas and carcinomas
88
Liquid tumor
Cancer of the blood including leukemia, lymphoma, myeloma
89
Top CRO companies
IQVIA
Icon
Paraxel
PPD - pharmaceutical product development
Covance
90
ECOG performance status scale
patient’s level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.).
91
ECOG scale
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5 Dead
92
Tumor marker
tumor marker is anything present in or produced by cancer cells or other cells of the body in response to cancer or certain benign (noncancerous) conditions that provides information about a cancer, such as how aggressive it is, what kind of treatment it may respond to, or whether it is responding to treatment
93
How are liquid tumors measured
Circulating tumor cell count (CTC)—circulating tumor cell counts are measured as the number of CTCs in a specified volume of blood. Results may be interpreted as favorable or unfavorable. Prostate, colon, and breast cancers all have unique cutoffs for when a CTC count is no longer favorable for
94
Adjuvant therapy
Adjuvant therapy is often used after primary treatments, such as surgery, to lessen the chance of your cancer coming back. Even if your surgery was successful at removing all visible cancer, microscopic bits of cancer sometimes remain and are undetectable with current methods. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.
95
Neoadjuvant therapy vs adjuvant therapy
Neoadjuvant chemotherapy is delivered before surgery with the goal of shrinking a tumor or stopping the spread of cancer to make surgery less invasive and more effective. Adjuvant chemotherapy is administered after surgery to kill any remaining cancer cells with the goal of reducing the chances of recurrence.
96
Liquid vs solid tumors
Solid tumours refer to a solid mass of cancer cells that grow in organ systems and can occur anywhere in the body, for example Breast Cancer. Liquid tumours occur in the blood, bone marrow or lymph nodes and include types of Leukaemia, Lymphoma and Myeloma.
97
How is anc found?
The ANC is found by multiplying the WBC count by the percent of neutrophils in the blood. For instance, if the WBC count is 8,000 and 50% of the WBCs are neutrophils, the ANC is 4,000 (8,000 × 0.50 = 4,000). When the ANC drops below 1,000 it is called neutropenia
98
RP2D
Recommended phase II dose- the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study
99
Two categories for lesions
Target and non target lesions.
There is a limit to the # of target lesions which may be selected at baseline. Target lesions shouldn’t exceed 5 total and no more than 2 lesions per organ
If there are excess lesions after the maximum number of target lesions has been reached, these excess lesions should be assigned as non-target lesions. Non-target lesions also include sites of tumor too small to qualify as target lesions and non-measurable metastatic disease
Non target lesions are qualitative but not quantified if too small
100
TNM system
Tumor, Nodes, metastasis
Stage 0: no cancer only abnormal cells with potential to become CA (carcinoma)
Stage I: CA is small and only in 1 area (early stage)
Stage II&III means the CA is larger and has grown to nearby tissue or lymph
Stage IV: CA has spread to other parts of the body (advanced or metastatic CA)
101
CSSRS & HDRS
Columbia suicidal severity rating scale
Hamilton Depression rating scale
Questionnaires used to assess participant before being enrolled in CNS study
102
CNS study
Neurology clinical research trials focus on diseases and conditions of the brain and nervous system such as Parkinson's Disease, Alzheimer's Diseases, multiple sclerosis
103
Carcinoma
Cancer that begins in the skin or in tissue that line or cover internal organs
104
Sarcoma
Cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue
105
Leukemia
Cancer that starts in the blood-forming tissue such as the bone marrow and causes large #s of abnormal blood cells to be produced and enter the blood
106
Lymphoma and myeloma
Cancer that begins in the cells of the immune system
107
Central nervous system cancers
Cancers that begin in the tissue of the brain and spinal cord
108
Benign tumors
Non cancerous. Often can be removed and in most cases don’t come back. Cells in benign tumors do not spread to other parts of the body
109
Malignant tumors
Tumors that are cancerous. Cells in these tumors can invade nearby tissue and spread to other parts of the body
110
feasibility questionnaire
Used in PQV aka SSV it’s the set of questions prepared by a study sponsor or contract research organizations (CROs) to identify the potential and interest of a site/investigator to run clinical trial feasibility successfully
111
ICF critical components
-make sure not expired
-signature of PI or SC is there
-protocol name and site correct
-no procedure has taken place before consent date
-each page is initialed
112
How do you prioritize time on site
-Review any newly enrolled subjects
-review any subjects with SAE
-drug accountability
-review subjects that I’ve already monitored
-meet w PI
-regulatory binder review
-provide snapshot of visit to the SC and schedule next visit
113
Nadir
Lowest value of measured tumor. When a person with cancer reaches their “nadir” following each chemotherapy cycle, it means that the person's blood cell counts are the lowest they will be during that treatment cycle.
114
Tumor burden
Aka tumor load
number of cancer cells, the size of a tumor, or the amount of cancer in the body
115
How did you start your career
As a clinical research coordinator at university of Illinois at chicago in 2011 after graduating with my bachelors in science
116
Duties of a CRA
-ensure integrity of clinical data
-wrote confirmation/follow up letters
-reviewed edc to ensure queries answered
-upload docs to TMF
-ensure IP accountability
117
Common Prostate Drugs
docetaxel, apalutamide, abiraterone
118
Dose escalation
study that determines the best dose of a new drug or treatment. In a dose-escalation study, the dose of the test drug is increased a little at a time in different groups of people until the highest dose that does not cause harmful side effects is found. A dose-escalation study may also measure ways that the drug is used by the body and is often done as part of a phase I clinical trial. These trials usually include a small number of patients and may include healthy volunteers
119
Examples of IRB
sterling, quorum, advarra, liberty
120
Drug compounding
the process of combining, mixing, or altering ingredients to create a medication tailored to the needs of an individual patient. Compounding includes the combining of two or more drugs
121
Endpoint
an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial
122
Sentinel dosing
is often practiced so that one person in the first cohort of participants is dosed in advance of the full study. This ensures that if adverse events manifest quickly, as few participants as possible are impacted.
123
Single ascending dose
participants are given a single dose of the treatment and are observed while confined for any clinically relevant adverse events or toxicity. If adverse events are not observed in a pre-determined number of participants, then the dose will be escalated to the next planned higher dose. This dose escalation will continue until a predetermined PK exposure safety level is achieved, or intolerable adverse events are experienced.
124
Multiple Ascending Dose
MAD trials usually follow SAD trials and are conducted to further assess the safety, tolerance and PK and PD of the NCE; however, participants within a single cohort will be given multiple doses at pre-specified intervals or at intervals and dose-levels informed by the data generated in the SAD trial. The dose levels and frequency of the doses are most often selected to achieve “therapeutic levels” which will be maintained for several days to enable safety or “activity” parameters to be monitored. It is common for three or more dose levels to be assessed.
125
PVP
Pharmacovigilance physician
126
SMP
Safety management plan
127
IRT
Interactive response system
128
NCS
Not clinically significant
129
PK
pharmacokinetic (PK) study of a new drug involves taking several blood samples over a period of time from study participants to determine how the body handles the substance.
130
Elements of ICF
Description of Clinical Investigation. ...
Risks and Discomforts. ...
Benefits. ...
Alternative Procedures or Treatments. ...
Confidentiality. ...
Compensation and Medical Treatment in Event of Injury. ...
Contacts. ...
Voluntary Participation
131
Cₘₐₓ
the maximum serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose
132
TEAE
Treatment emergent ae
While the treatment emergent AEs refers to adverse events temporally related to the study treatment, the drug-related AEs refers to the causality assessment by the investigator.
133
EDiary
is available to subjects via login to a mobile device for daily observations and has the added benefit of improving data collection eDiary responses through reminders and alerts.
134
CTA
Clinical Trial Agreement : legally binding agreement that governs the conduct of a particular study and sets forth the obligations of each party to the agreement.
135
CTA
Clinical Trial Agreement: legally binding agreement that governs the conduct of a particular study and sets forth the obligations of each party to the agreement.
136
indemnification
compensation for harm or loss.
security against legal liability for one's actions
137
DCF
Data clarification form
