Clinical Research 101
•Selecting the investigator(s)
•Providing investigator(s) with the necessary information to conduct the clinical trial
•Ensuring proper monitoring of the clinical study
•Ensuring that the clinical study is conducted in accordance with Good Clinical Clinical Practice(GCP)
What are the responsibilities of a Sponsor?
At the conclusion of an inspection, this is presented and discussed with the company’s senior management, regarding objectionable conditions.
What is a 483?
•1572
•Delegation of Authority Log
•Financial Disclosures
•CVs, Medical Licensure
•Protocol(s)
•Investigator Brochure(s)
•Investigational Product Management Documentation
•Clinical Trial Agreement
•Monitoring/Auditing Reports
• IRB Submissions/Approvals
•Study Correspondence
•IND/IDE approval by FDA, if applicable
•Normal Value Range(s) for Laboratory tests
•Subject Enrollment Log Source Documents
What are Essential Documents?
1. Schedule monitors the times that you are available (if you normally get in the office at 8:30, don’t schedule an 8am monitoring visit if you aren’t able to make it by that time)
2. Give your monitor a time that you are available to meet and discuss findings (don’t feel like you must sit with them the entire time they are onsite)
3. Prior to the monitor visit, ask them for a confirmation letter that lists the things that will be reviewed (this allows you to properly prep and will avoid having you run around during the visit collecting things at the last minute)
What is setting boundaries for your monitor?
What are milestones triggered automatically?
An individual who conducts a clinical investigation or, in the event of an investigation conducted by a team of individuals, is the responsible leader of the team
What is a principal investigator (PI)?
Sponsors, CROs, Investigators, monitors, IRBs, medical monitors, study team, and others.
Who is responsible for GCP compliance?
The Investigator commitment that he or she will personally conduct or supervise the described investigations is reflected on this document
What is a 1572?
1. Review monitor follow-up letter and resolve action items prior to upcoming monitor visit.
2. Ensure the maintenance of regulatory binder is up to date (all documents are updated and filed appropriately)
3. Review EDC, source, DOA, etc
What is monitor visit preparation?
What are milestones that require site action?
Review and Verify - validity of CRFs, source docs, DOAs, subject eligibility, protocol compliance, ICFs, etc.
What is the role of a monitor (CRA)?
It is related to a commitment made in FDA Form 1572. Many investigators do not appear to realize the implications of signing this form in terms of their commitment.
What is a top reason an FDA 483 warning letter is given to a PI?
The principal investigator (PI) is responsible to maintain a ‘List” of appropriately qualified persons to whom significant trial-related tasks have been assigned (ICH section 4.1.5). This document should be continuously updated and filed in reg binder?
What is a DOA?
•Update screening/enrollment log
• Verification of all consents
• Assure lab, EKG, diagnostic and radiology reports have been reviewed and signed by PI (especially if values are out of range or abnormal findings)
• Ensure all deviations or missing information is well documented
Ensure AE logs and con-meds
What is reviewed during a monitor visit?
What is ongoing subject management?
- Voluntary Participation
- Informed Consent
- Minimization of Risk
(Past transgressions lead to the need for laws that protect the rights and welfare of human subjects.)
What is Nuremberg Code (1947)?
1.Conduct and supervision of clinical trials
2.Maintenance of accurate case histories
3.Informed consent
What are the top 3 reasons for a 483?
When items are submitted and receive approval, the submission as well as the approval letter should be filed in regulatory binder,
What is IRB Documentation?
•Review progress of clinical trial and ensure protocol adherence and regulatory compliance while maintaining the rights, safety and well-being of subjects
•Frequency is dictated by complexity of the study and Sponsor requirements
•Investigator and key research personnel should be available for questions
What is the purpose of a Monitoring Visit?
What is monthly Finance Check?
1. Researchers test a drug or treatment in a small group of people (20–80) for the first time. The purpose is to study the drug or treatment to learn about safety and identify side effects
2. The purpose is to determine the right dosage and effectiveness in treating that particular disease. This testing normally takes place with a larger number of volunteers who have the disease (100-300).
3. The purpose is to determine whether the treatment would be safe and effective for a wide variety of people. The plan normally involves randomizing (assigning) participants to treatment or control groups (placebo). There can be more than one treatment group, especially if the treatment involves a combination of drugs or different components.
4. Post-Market: After a drug is approved by the FDA and made available to the public, researchers track its safety in the general population, seeking more information about a drug or treatment’s benefits, and optimal use.
What are the 4 phases of a clinical trial
1. Data Integrity - False Information (false CRFs, consents, or reports)
2. Missing ICFs
3. Ineligible subjects enrolled
4. Unreported SAEs
5. Missing signed docs such as 1572, protocol, Investigator agreement,
What are examples of FDA findings?
A committee of experts responsible for reviewing clinical trial data on an ongoing basis to ensure the safety of study subjects and validity and integrity of the data. Their reports must be submitted to the IRB and filed in the regulatory binder.
What is a Data Safety Monitoring Board (DSMB)?
BSWRI facilitates sponsor conduct of monitoring visits to ensure that investigators are compliant with the clinical protocol and GCPs, data are of high quality and integrity, and the facilities and staffing are adequate for continued participation in the study. T his SOP outlines the activities required for facilitating monitoring visits during a clinical trial through the research areas at BSWRI.
What is BSWRI SOP for monitoring visits?
When CTMS data is entered and we trigger payment from sponsor. They will deny the invoice if data isn't accurate in this portal.
What is, sponsor pays invoices based off what is entered in EDC?