Med Sci CRM Exam 2

Sponsor/investigators (the same person is the sponsor and the PI) are most often seen in which context?

University hospitals

In practical terms, the site records of a biomedical study are usually kept for how long, and in what way?

Indefinitely. They need to be kept in a system that allows for document identification, search, and retrieval.

<> IRBs are generally faster to review applications and may have specific expertise on the study type being conducted, but they are also usually very expensive.

Independent

Centralized monitoring involves the review of <>, not just reviewing data from a central location.

centralized data

The sponsor should create a <> that lays out the plan for interim monitoring visits.

clinical monitoring plan (CMP)

The Office of <> provides direction, assistance, management and oversight of field import operations, including investigational and compliance activities.

Enforcement and Import Operations

What should the CRA be sure to address during the SIV?

- Review applicable regulations - Clarify protocol requirements - Discuss the process of implementing the protocol at the site

What kind of things does an IRB handle during an ongoing study?

- Review protocol amendments - Review consent form changes - Review additional ads - Review sponsor and annual reports

What does the IRB do after the completion of a study?

- Review the study termination report - Review study record-keeping

The PI is responsible for ensuring that their investigation is conducted according to which three things?

- Signed investigator agreement - Investigational plan, or protocol - Any applicable regulations

What are some considerations for site qualification assessed by the CRA during an SQV?

- Does the investigator have research experience - Has the PI done previous research in the therapeutic area - Has the PI handled studies of this type and complexity before - Were previous study enrollment targets met - How many subjects completed previous studies - Are there other studies at this site/will the staff be too busy to handle our study if we choose this site

What are some of the pros and cons that have to be weighed when selecting an independent IRB?

- Institutional policies - Industry awareness - Local community knowledge - Timeliness of review - Cost

The site and sponsor must keep their clinical trial records for how long? What about the IRB?

- 2 years after last marketing action - 3 years after research completion

What is included in an IRB's record keeping?

- Correspondence - Meeting minutes - SOPs - Membership list - Submitted and approved documents

What is the overarching primary job of the PI?

To protect the rights, safety and welfare of the study subjects.

While doctors new to research will not necessarily be turned away during a site qualification visit, they may require -

additional training and oversight beyond what is standard

When many sites on a study use the same independent IRB, that IRB is called a -

central IRB

The site qualification visit must occur prior to <>.

site startup

ICH E6 defines a <> as any individual member of a clinical trial team designated and supervised by the investigator at the trial site to perform critical trial-related procedures and to make important trial-related decisions.

sub-investigator

The <> plays a role in counterterrorism by responding to public health threats and ensuring the safety of the food supply.

FDA

T/F: Since the facilities and laboratory equipment are checked during qualification, the CRA does not need to recheck them at the initiation visit unless the sponsor specifically requests it.

False

T/F: When a study is completed, the PI's duty of record keeping also ends.

False

It is OK for a Sponsor to transfer some obligations to a Contract Research Organization verbally. A. True B. False

False (must be done in writing)

T/F: Since they have higher standing, education, and relevant experience than low-ranking members of the clinical trial team (like technicians), sub-investigators may assume official responsibility for certain key tasks, such as ensuring that all human subjects have been properly consented.

False - the buck stops with the PI, no matter what, every single time.

T/F: All study monitoring must be done in-person.

False, for some studies remote monitoring is allowed

T/F: If a drug, device, or biologic is to be marketed outside of the US, no additional oversight is required, as the US FDA process is considered the gold standard internationally.

False. Marketing outside of the US requires going through the country of interest's approval process.

The Office of <> provides advice and counsel to ORA and FDA leaders regarding medical device and radiological health program operations, including emergency response activities.

Medical Device and Radiological Health Operations

In the FDA, immediately under the office of the commissioner are which two offices?

Office of Medical Products and Tobacco, and Office of Global Regulatory Operations and Policy

Under the Office of Global Regulatory Operations and Policy is which office?

Office of Regulatory Affairs

Which member of the research team is responsible for the conduct of the study and the other research team members?

Principal Investigator (PI)

What is the function of CDER?

Regulates OTC and prescription drugs.

What is the function of CBER?

Regulates biological products for human use under applicable federal laws.

The Office of <> inspects regulated products and manufacturers, conducts sample analyses of regulated products and reviews imported products offered for entry into the United States.

Regulatory Affairs

<> allows for proactive oversight of data consistency, completeness, and distribution pattern without having to visit the data site.

Remote monitoring

If a site and a sponsor have worked together in the past, parts of the site qualification visit may occur in what context?

Remotely

<> help determine when a risk might turn into an actual issue.

Risk indicators

If the PI of a biomedical study is not a physician, how should the PI ensure that medical decisions in the study are arrived at competently?

There should be a physician in a sub-investigator position who is responsible for medical decisions in the study

The <> Program is a rigorous compliance and enforcement program aiming to ensure that the tobacco industry follows the law and regulations designed to reduce the health burden of tobacco use.

Tobacco Operations

T/F: Although the PI is ultimately responsible for all record-keeping, everyone on the trial staff has a duty to contribute to keeping good and complete records.

True

IRBs can be one of two types: <> and <>.

institutional, independent

What is the most common type of monitor visit to the site by the CRA?

interim monitoring visits

The sponsor is responsible for monitoring the progress of a clinical investigation. In order to meet this requirement, the CRA will conduct <>.

interim monitoring visits (IMVs)

The IRB should be composed of medical, scientific, and <> members.

non-scientific

Risk-based monitoring provides sponsors with the ability to evaluate and plan for risks before a study starts and continuously adapt monitoring activities to areas that have the most potential to impact <> and <>.

patient safety, data quality

The specific manner of record-keeping should be outlined in the <> and adhered to consistently.

protocol/study plan

Once the site is <>, they will then be initiated and begin recruiting subjects.

qualified

It's important to remember that while a PI can delegate tasks, they cannot delegate <>.

responsibility

Monitors ensure that all report forms perfectly match the original source recording, in a process known as <>.

source document verification (SDV)

The term <> refers to refers to the entity who takes responsibility for the initiation, management, and/or financing of a clinical trial.

sponsor

Throughout the study, the <> verifies that the site is meeting its duty to maintain proper records.

sponsor

T/F: Typically, if performing research through a university, researchers must use the university's IRB.

True

T/F: A candidate site can remove themselves from consideration during a site qualification visit should they choose to.

True. Done is the sponsor is difficult to work with, or the sponsor does things the site doesn't agree with or condone.

What are the responsibilities of the CRA (aka clinical trial monitor)?

- Acts as a line of communication - Verify qualifications and resources of investigator - Verify accountability for the investigational product - Ensure site compliance - Verify informed consent and subject eligibility - Review and verify source documents and CRFs - Ensures proper reporting of adverse events and serious adverse events - Communicate data deviations

Aside from deciding which new drugs, devices and biologics are allowed on the market, what are the activities of the FDA?

- Develops and enforces regulations - Issues information and guidelines - Inspects products, facilities, and research entities - Regulates labeling, promotion and processes through which evidence of safety and efficacy are developed

In addition to ensuring SDV, what other duties does a monitor have?

- Look for data entry errors and missing data - Assess compliance with the protocol - Look into investigational product accountability - Evaluate investigator supervision

What has allowed for more remote monitoring as opposed to in-person monitoring only?

- Technology allows it to occur - The push to get new drugs/devices/biologics studied, reviewed and approved faster

What are the three key ideas in risk-based monitoring?

- The sponsor assesses the risk at the protocol, program, and site level - The sponsor determines the critical data and processes of the trial - The sponsor defines the monitoring approach with an integrated quality risk management plan

According to ICH E6 part 8, the site is required to retain certain documents. Name several things which must be retained.

-everything submitted to the IRB -all regulatory correspondence -general correspondence -IRB reports and acknowledgement of receipt -Any documentation of protocol deviations -Safety reports -Informed consents

What are four categories of staff representing the sponsor during a study?

1. Clinical and safety staff 2. Informatics/IT staff 3. Regulatory affairs staff 4. Manufacturing staff

How long must an IRB keep records on a study?

3 years after research completion

All individuals involved in clinical research have a role in: A. Helping to develop safe and effective therapies while ensuring the rights, safety, and welfare of the subjects have been protected. B. Ensuring that the FDA audits every single research site. C. Assisting the data managers in the final analysis of the data sets. D. Generating clean data while ensuring that the sponsor earns as much revenue as possible.

A

How does the clinical trial monitor ensure compliance with FDA mandated regulation for the control of an investigational product? A. By ensuring that a site is properly trained on the storage an maintenance of the investigational product B. By providing the site with the FDA approved investigational product accountability logs C. By not allowing anyone other than the PI handle the investigational product at the site D. By doing an investigational accountability check before the site gets sent the investigational product

A

In which field are product development timelines typically shorter? A. Medical Device B. Biologic C. Drug

A

The best recommendation for a potential investigator in a phase III diabetic clinical trial is a physician who has: 1. A private practice with a limited patient base 2. High interest but little time for clinical trials 3. Applied for board certification in endocrinology 4. Received an inspection report 5 years ago citing missing SOPs A. 3 and 4 only B. 1 and 3 only C. 2 and 4 only D. 1 and 2 only

A

What should a sponsor do when they discover a PI is not complying with the general investigational plan? Choose the best answer. A. Promptly secure compliance or discontinue shipments of investigational new drug B. Call all the subjects at that site and ask them about their experiences with the PI on the trial C. Document the noncompliance and continue the study as planned D. Immediately notify the FDA and start a federal investigation into the qualifications and misconduct of the PI

A

You are a Principal Investigator looking to hire a new Clinical Research Coordinator for your site, which has 7 ongoing studies. You interview two candidates. Jane Parrish arrives on time but has misplaced her resume. She has been a coordinator for 10 years. Jane is an extrovert and loves building new relationships and contacts with sponsors and subjects. She prefers to work under tight, direct supervision with heavy handed management and does not like to multitask. Patrick Snipes arrives on time and has brought his resume in a neatly organized packet detailing his accomplishments in his past 2 years as a coordinator. Patrick is an introvert, but details many instances of building close, trusting relationships with sponsors and subjects. He works well independently and enjoys taking on studies which have active and aggressive timelines. He prides himself on his knowledge of and adherence to GCP. Who is the better choice to be your new coordinator? A. Patrick Snipes B. Jane Parrish

A

You are the project manager helping the Sponsor to select a site for your research study. This study is a pediatric oncology trial. You have four options. Dr. Harrison has 45 years of experience in breast cancer clinical trials. Dr. Welch has been doing pediatric clinical trials for the last 24 years and specializes in podiatry. Dr. Gui has 15 years of experience in pediatric oncology, has a masters in clinical research management, and has been doing clinical trials for 2 years. Dr. Staples has 1 year of experience in pediatric oncology and has never been involved in a clinical trial. Which PI would be the best choice to participate in your trial? A. Dr. Gui B. Dr. Staples C. Dr. Harrison D. Dr. Welch

A

If a site's preliminary data review indicates that the site is a promising candidate for becoming a study site, what's the next step taken?

A site qualification visit by the monitor/sponsor

What is the function of CDRH?

Assures safe, effective, and high-quality medical devices and radiation-emitting products.

The Office of <> consists of a specialized workforce that conducts inspections, investigations, and compliance activities for blood and tissue products as well as vaccines and other biological products regulated by the Center for Biologics Evaluation and Research.

Biological Products Operations

The Office of <> is responsible for cross-center activities ensuring the protection of subjects involved in clinical trials for FDA-regulated products and that non-clinical research is conducted according to Good Laboratory Practices (GLP) requirements.

Bioresearch Monitoring Operations

What is the purpose of clinical trial monitoring? A. Ensure subjects are being compensated, ensure reliable data, and ensure IRB approval of the trial B. Ensure subject protections, ensure IRB approval, and ensure that the PI has no financial conflict of interest C. Ensure subject protections, ensure reliable data, and ensure compliance D. Ensure compliance, ensure subjects are being compensated, and ensure that the PI has no financial conflicts of interest

C

Which document demonstrates that the PI has the education, training, and experience to be an expert in the clinical investigation of the drug under investigation? A. Statement of Investigator B. Clinical Protocol C. Curriculum vitae (CV) D. Form FDA 1572

C

Who is responsible for selecting qualified monitors? A. The PI B. The IRB C. The sponsor D. The FDA

C

During the site initiation visit (SIV), the <> will ensure that the site is ready to begin enrolling subjects.

CRA

The <> is responsible for submitting the monitoring visit report at the end of a monitoring visit.

CRA

The <> is tasked with completing the site qualification visit and relaying the results back to the sponsor.

CRA

Which sponsor representative defines goals and requirements for the trial, motivates and keeps staff on track for a timely study completion, and helps plan and execute the study?

Clinical Project Manager (CPM)

Which sponsor representative acts as the "eyes and ears" of the sponsor agency, and assures subject protection, monitors compliance with guidelines, ensures product accountability, verifies CRF data against source documents, and ensure complete regulatory documentation?

Clinical Research Associate (CRA)

Which research team member acts as a liaison between the PI and the sponsor?

Clinical Research Coordinator (CRC)

Which research team member is focused on the smooth day-to-day operation of the study, and assist the PI in implementing the research protocols?

Clinical Research Coordinator (CRC)

A <> is a person or company that assumes, as an independent contractor with the sponsor, one or more of the obligations of the sponsor.

Contract Research Organization (CRO)

According to the article, which non entry-level clinical research role needs to be able to point out the deficiencies related to the work of others and hence must not be adverse to conflict? A. Biostatistician B. Principal Investigator C. Clinical Research Coordinator D. Quality Assurance Auditor

D

For how long must the investigational site retain records if the drug under study is not approved for the study indication? A. Indefinitely B. 5 years after the investigation is discontinued and FDA is notified C. 2 years after closure of the study at the site D. 2 years after the investigation is discontinued and FDA is notified

D

Who has the responsibility to protect human subjects? Choose the best answer. A. CRAs B. Principal Investigators C. Coordinators D. All people involved in clinical research

D

Per regulations, for how long must a study's site records be kept?

For two years after the last marketing action is taken on the thing being studied.

What is typically the first step in selecting a trial site?

Gather preliminary data. This entails examining a site's past work and experience, and looking into their available resources to make sure the site is qualified and able to generate high-quality data and recruit study participants.

The Office of <> provides advice and counsel to ORA and FDA leaders regarding human and animal food products, field operations, and emergency response activities.

Human and Animal Food Operations

The SIV occurs after the site has received <> approval for the study and the investigational product has been shipped by the sponsor.

IRB

The Office of <> provides advice and counsel to ORA and FDA leaders regarding pharmaceutical products field operations and emergency response activities.

Pharmaceutical Quality Operations

<> is a newer monitoring style that recognizes that a lot of time is spent monitoring information and processes that have little impact on the overall outcome of the study or on subject safety.

Risk-based monitoring

The <> is the opportunity for the sponsor to communicate to the site what their expectations are and how the site can be successful.

SIV

The <> is an opportunity for the sponsor to assess whether or not the site is qualified to conduct the study.

Site qualification visit

The <> should be an open, two-way street that encourages questions, dialogue and flexibility.

Site qualification visit

Which entity determines the appropriate nature and extent of monitoring?

Sponsor

Obtaining informed consent, maintaining records, reporting findings, and reporting updates back to applicable regulatory authorities are all responsibilities of which member of the research team?

The PI

Define "clinical trial monitoring".

The act of overseeing the progress of a clinical trial and ensuring that it is conducted in accordance with the study protocol, applicable SOPs, GCP, and regulatory requirements.

T/F: Some studies require more intensive monitoring, and others can take a more relaxed approach.

True

T/F: Delegating tasks to a CRO does not absolve the sponsor of their official responsibilities.

True

T/F: FDA is allowed to inspect the sponsor or the site at any reasonable time.

True