Operationalizing Clinical Trials
Operationalizing Clinical Trials
Slide set: File:Clinical Research Organizations.pdf

# Overview
Clinical trials, also known as clinical studies, test potential treatments in human volunteers to see whether they should be approved for wider use in the general population. A treatment could be a drug, medical device, or biologic, such as a vaccine, blood product, or gene therapy. Potential treatments, however, must be studied in laboratory animals first to determine potential toxicity before they can be tried in people. Treatments having acceptable safety profiles and showing the most promise are then moved into clinical trials. Although "new" may imply "better," it is not known whether the potential medical treatment offers benefit to patients until clinical research on that treatment is complete. Clinical trials are an integral part of new product discovery and development and are required by the Food and Drug Administration before a new product can be brought to the market.

# STUDY MANAGEMENT:

## CLINICAL RESEARCH ORGANIZATIONS:
CROs: Why Do We Need Them?
- Limited resources/Augment in-house personnel
- Access to large number of patients/sites
- Accelerated projects
- Development cycles of products
- Increased products in the development pipeline
- International studies
- Joint collaborations
- Marketing Support
CROs: How Do We Choose Them?
- Ownership structure
- Independent, Confidential
- Financial stability
- Professionally staffed
- Experience
- GCP, Global regulatory experience, International standards
- References
- Specialization
- Standard Operating Procedures
- Match between Sponsor and CRO
- Quality assurance
- Infrastructure
- Location, International network, Data security, Electronic  database/Communication

# Clinical Trials and Human Subject Protection
Adherence to the principles of good clinical practice (GCP), including human subject protection (HSP), is universally recognized as a critical requirement to the ethical conduct of research involving human subjects. The Office of Good Clinical Practice (OGCP) serves as the FDA focal point for GCP and HSP issues related to FDA-regulated clinical trials. OGCP sets priorities for the development of GCP and HSP policy, works to ensure consistency in GCP and HSP policy across the agency, participates in international GCP and HSP harmonization activities, and serves as liaison to other Federal agencies and external stakeholders committed to the protection of human research participants.

# Bioresearch Monitoring
FDA uses Compliance Program Guidance Manuals (CPGM) to direct its field personnel on the conduct of inspectional and investigational activities. The CPGM's described below form the basis of FDA's Bioresearch Monitoring Program. The purpose of each program is to ensure the protection of research subjects and the integrity of data submitted to the agency in support of a marketing application

## Common Clinical Investigator Observations
- Failure to conduct an investigation in accordance with the signed investigator statement or agreement/investigational plan/applicable regulations
- Inadequate or inaccurate case histories
- Investigators subject records inadequate
- Inadequate drug/device disposition records
- Failure to obtain informed consent in accordance with Part 50

## Common IRB Observations
- Inadequate meeting minutes
- Inadequate membership rosters
- Inadequate initial and continuing review of research
- Inadequate written procedures for prompt reporting of non-compliance, suspension or termination
- Quorum issues

## Common Sponsors, Contract Research Organizations, Monitors Observations
- Failure to ensure proper monitoring
- Failure to ensure the investigation is conducted in accordance with the general investigational plan and protocol(s)
- Failure to secure compliance or terminate an investigators participation in the investigation
- Failure to ensure the FDA/IRB/investigators are informed of significant new information or significant new adverse effects

## Common Bioequivalence Observations
- Recordkeeping
- Blinding Codes
- SOPs
- Inclusion/exclusion criteria issues
- Analytical concerns:
- Validation
- Stability
- Chromatography
- Calibration Curve