CRA study guide pt !
INDA Definition
Application filed with the FDA after completion of pre-clinical and prior to human testing.
Sample Size - Phase I
20-80
Every Clinical Investigation begins with the development of
A Protocol
What is a Protocol
A document describing how the Clinical Trial will be conducted and ensures the safety of the trial subjects, and integrity of the data collected.
What are source documents?
A source document is a document in which data is collected for a clinical trial is first recorded
What is the Pre-Clinical phase?
A study to test a drug, procedure, or another medical treatment in animals
What is a Trip Report?
A trip report is an annotated report which details the visit conducted by the CRA It is comprised of several questions regarding the visit
Design: Double - Blind
Double - Blind is where neither participant nor experiements know who is receiving drug. Only Sponsor knows DB is used to prevent bias due to demand characteristics or the placebo effect.
Where is the Visitor Confirmation Letter located?
In the ISF with P.I.'s signature of initials, and date confirming he/she reviewed --be sure to send confirmation letter before every visit--
Why should site file a NTF
Instruct site to notify sponsor and keep you the CRA in copy
Acronym: INDA
Investigational New Drug Application
Because No drug is completely safe, what is important?
It is important to estimate the risk associated with exposure to the chemical under specified conditions by performing appropriate tests.
Popoulation of Phase IV
Mixed
NDA: Definition
NDA is an application filed with the FDA for sale and marketing of the drug product
The most performed Clinical Trials evaluate ---
New drugs Medical devices (drug-eluting stent, insulin pen) Biologics (blood, vaccines, tissues) Psychological therapies or other interventions
When is the Confirmation Letter sent
Once CRA schedules an onsite monitoring visit, depending on the time outlined on the monitoring plan
What does "Randomize" mean
One Group is assigned to an experimental group and one group is assigned to a controlled group (You don't know what group you will get assigned to)
When does the visit occur
Pre-Qualification (PQV) occurs once a site has been identified by the CRO or sponsor
Types of Visits
Pre-Qualification Visit (PQV) Site-Initiation Visit (SIV) Routine Monitoring Visit (RMV) Close Out Visit (CIV)
Usually, Confirmation Letters are addressed to_________, and sent to ______, to be ________
Principal Investigator, Study Coordinator, filed in the Investigator Site File (ISF)
When does this visit occur
SIV (Site Initiation Visit) occurs once the site has been selected to participate in the study and the site has provided all approvals and regulatory documents have been submitted
Design: Single - Blind
Single - Blind is used with a placebo. Subject is unaware if they're receiving study drug or placebo. Study Team knows if subject has drug or placebo.
What are the steps if a Temperature Exclusion occurs
Site should fild NTF to indicate what occured, i.e. why did the temperature excursion occur what was done what can be done to prevent further temperature excursions
What effects can happen from bias drug groups
Skews the data
SDV vs SDR:
Source Data Review - When data in the subjects chart is reviewed Source Data Verify - When the data that is being reviewed is cross referenced to what the site has entered into the EDC
When do you used the Subject Logs? (drug accountability)
When SDV'ing the drug eCRF pages. You will be confirming that whatever amount is listed in the EDC is recorded on the subject drug dispensing log
Most TR questions require this type of response
Yes or No response
What is a Temperature Exlusion
a Spike or Drop in the temperature of storage location
What does an INDA contain:
pre Clinical data: Animal Pharmacology Toxicology Studies
Randomization prevents:
preferential drug or placebo administering (I cant assign my friends to experimental group, because I want them to get the drug. Can not assign by sex, race)
INDA: Unless the FDA--
specifically objects, the IND is automatically allowed after 30 days and clinical trials can begin
What does the Confirmation Letter outline?
the Confirmation Letter outlines an agenda or the topics you plan to address during visit
The Protocol Document describes what aspects of the Clinical Trial?
the objects the design the methodology statistical considerations organizations of a Clinical Trial
What if a temperature exclusion is noted
the site should be instructed to quarantine the drug (remove the affected drug until further instruction is received)
How many visits per study
Visits occurs once per study site
Each Study's Trip Report comes with
annotated guidelines which provide instructions on how to answer the questions within the TR
Some Confirmation Letters might also list --
lists outstanding action items from the previous visit, that requires follow-up or resolution during your visit
No chemical can be certified as completely---
"Safe". Every chemical is toxic at some dosage.
What to collect for Drug Accountability
1. A copy of the Drug Accountability inventory, subject, and destruction logs are collected 2. A copy of the month's temperature logs are collected 3. Drug shipping packing list
What does Drug Accountability require the Monitor to confirm?
1. Drug is being stored within the specified temperature parameters 2. The correct dosage was given to the subject 3. The drug has not expired 4. The used drug has been destroyed or shipped back to the sponsor
Source Data Verification: Purpose of SDV
1. Is a process to evaluate the conformity of the date presented in CRF (Edc system) 2. to ensure data collected are reliable and allow reconstruction and evaluation of the study
What info is reviewed through an NDA
1. Is drug safe and effective in it's proposed use as directed, and do benefits outweigh the risks? 2. Is drug's proposed labeling (package insert) appropriate, and what should it contain? 3. Are the methods used in manufacturing (GMP) the drug and the controls used to maintain the drug's quality adequate to preserve the drug's identity, strength, and purity?
Different types of Source Documents?
1. Original Paper Documents 2. EMR record 3. or Certified copies of the EMR
Purpose of Monitoring
1. to educate study staff on drug handling protocol procedures: GCP, safety reporting, and ethical issues 2. Maintain temporal sequence of event (to follow the study of assessments) also termed: Contemporaneous 3. Adherence to protocol, GCP, SOP, Regulatory and Data Cleanliness 4. To ensure consistency 5. To prevent fraud
Sample Size - Phase lll
100-1000
Sample Size - Phase ll
100-200
Sample Size - Phase IV
1000 +
Design: Open
Both the investigators and the subjects know what is being given. There is no placebo
SD: This data is later entered in _____
Case Report Form
Purpose of Clinical Trials?
Clinical Trials are conducted on human volunteers to allow safety and efficacy data to be collected for health interventions.
What does the Confirmation Letter confirm
Confirms the visit day and time previously agreed on
Perform Drug Accountability
Drug Accountability is completed by 1. taking an inventory of the Drug Supply (How much drug is on hand-What is the expiration date of drug) 2. collect lot/batch of each vial or bottle on site and total up your count. You will need this info for your Trip Report
What is Drug Accountability
Drug accountability is record keeping associated with storage, inventory, dispensation and destruction of the investigation Product (IP) used in Clinical Trials
Number of Clinical Trial Phases?
Four (4)
Number of Visits
Four (4)
Acronym: GMP
Good Manufacturing Practice
Population of Phase l
Healthy Volunteers
In Drug Accountability: Each site is provided with what?
Sponsor specific drug logs to log the amount of drug received for the site and subjects logs to log the amount of drug being dispensed or administered to the subject, and destruction logs to log the amount of drug used/dispensed
Population of Phase ll
Target Disease Patients
Population of Phase lll
Target Disease Patients
Who/What does most "randomizatoin"
The Computers
When is an NDA submitted
The NDA is submitted after completion of Phase l, ll, and lll studies of Clinical Trials
What is the purpose of a CRA
The Purpose of a CRA is to monitor Clinical Trials.
Purpose of Routine Monitoring Visit
The RMV is to ensure that the site is adhering to all study procedures
What is the aim of the Pre-Clinical phase?
The aim is to collect data in support of the safety of the new treatment
When does this visit occur
The first RMV is typically conduted two weeks after the first subject has been enrolled / randomized. Guidelines for scheduling monitoring visits shall be determined according to stage of of development, complexity of study, rate of subject accrual and other factors
Who are CRAs?
They are health professionals who perform many activities related to medical research, particularly Clinical Trials.
# of Principles in GCP
Thirteen (13)
Purpose of a Pre-Qualification Visit (PQV)
This visit is to determine whether the site meets the standard qualification to conduct the study
How many SIV visits per study
This visit occurs ONE (1) time per site per study
How many RMV per study
This visit occurs multiple times throughout the study at each site
How many visits per study?
This visit only occurs 1 time per site per study
Purpose of Site Initiation Visit (SIV) : -In Short:
To ensure PI and all research team assisting in the conduct of clinical research are informed about their obligations and responsibilities as they pertain to GCP, Investigational plan, applicable regulations, guidances and institutional policies. - The SIV prepares the site to conduct the research study
Acronym: TR
Trip Report
When does Close Out Visit occur
Visit is conducted at Termination of study, unless enrollment closes for the study and the site never enrolled a subject
When you get onsite, one of the things you might want to look for is?
Visitor Confirmation Letter that you previously sent
Purpose of Close Out Visit -- In short
to ensure that things are neat and tidy at the study site, and that the documentation is well organized and will remain in-tact and accessible in the future as needed, for regulatory reasons -To confirm sites obligations to the sponsor have been met, and any post study obligations are understood as well as followed through on.
Oftentimes, the Clinical Trial Leader or Project Manager will prepare-
will prepare a Template that you can use to draft your Confirmation Letter
