Development and implementation of effective CAPA's clinical trials should include the following elements: 

Identification of Issue

• Identify issues or non-compliance during audits, monitoring visits, or self-assessment, and document in the study record. 

Investigation and Root Cause Analysis

• Investigate the root cause using tools like the "5 Whys", a method of "digging deeper" into a problem by repeating the question "Why" five times after each posssible cause to fully understand contributing factors and to ensure the ultimate root cause is identified. 

Corrective Action Development

• Develop a detailed CAPA plan outlining both short- and long-term corrective actions, responsible individuals, and timelinese. 

Implementation

• Implement the paln by allocating appropriate resources. updating procedures, and providing/documenting any necessary training. 

Monitoring and Follow-up

• Monitor CAPA effectiveness over time through follow-up reviews to ensure issues are resolved and do not recur. 

Documentation and Reporting

• Document and report all CAPA Activities in the study file and submit reports to the IRB or sponsors, if required. 

UUSOP-07-A: Corrective and Preventative Action (CAPA) Plans

Adverse events should be collected and documented for each study participant on an AE log or within source documents. Each AE should be individually reviewed with signature and date of the Principal Investigator (PI) or Sub-Investigator (Sub-I). PI signature and date at the bottom of each page of an AE log should only be completed at the conclusion of study participation. Assessment of each AE should include the following:

• Severity: Intensity of the AE
• Attribution: Relationship to study drug/intervention
• Expectedness: Was the AE expected?
• Seriousness: Does the AE meet SAE criteria?
• Dose Limiting Toxicity (DLT), if applicable

The AE Log Template below is located in the OQC Toolkit and available to research teams to download and adapt for their own use. 

 
 

It is recommended to review the current IRB approved protocol for additional safety event evaluation criteria requirements.

Eligibility criteria are the specific requirements that potential participants must meet prior to enrollment into a research study. Eligibility is based on inclusion/exclusion criteria and is required to be followed when determining eligibility.

Research teams should review the following questions PRIOR to enrollment/randomization to help ensure the safety of research participants.

• Is the most current IRB approved protocol version being used to determine eligibility?
• Have each of the IRB approved eligibility criteria been reviewed and signed off by the Principal Investigator (PI) or Sub-Investigator (Sub-I)?
• Is any eligibility criterion pending? (e.g. labs, diagnosis, etc.)
• Are screening labs and/or imaging and diagnostic reports documented as reviewed by the PI/Sub-I or a medically qualified designee?
• Has the PI/Sub-I answered "yes" to any exclusion criterion?
• Is source documentation for all eligibility criteria filed within the participant chart? (e.g. specific labs, assessments etc. must be provided as evidence for validation)
• Were screening procedures completed within the protocol required timeline?
• Is there documentation confirming eligibility status that has been signed and dated by the PI/Sub-I? 

When a research study involves children, additional safeguards apply to protect their rights and welfare.  The University of Utah IRB provides the following guidance on the essentials of parental permission and child assent:

Parental Permission: 

• Before including a child in research, written permission from their parent(s) or legal guardian(s) must be obtained, unless the IRB has specifically waived this requirement. The number of parents required to give permission depends on the study’s risk category:
• Minimal risk or greater than minimal risk with direct benefit: The IRB decides if one or both parents are needed.
• Greater than minimal risk without direct benefit or not otherwise approvable research (45 CFR 46.406 & .407): Permission from both parents is typically required.

Child Assent:  

• Assent means the child’s affirmative agreement to participate. The IRB generally requires assent from children 7 years and older, though this depends on:
• The child’s age
• Maturity
• Psychological state
• Or if a child is cognitively unable to assent due to condition or disability.
• The plan for obtaining and documenting assent must be described in the study application. The University recommends separate, age-appropriate assent forms for:
• Younger children (7-11 years)
• Older children (12-17 years)

When a Child Turns 18

When a child reaches the legal age of consent while participating in research, informed consent MUST be obtained to continue. This requirement applies to registry studies where data is still being collected and submitted.  

Conducting a clinical trial with an investigational drug as a sponsor-investigator? You may need an IND application under FDA regulations (21 CFR 312.3).

Here’s what you need to know:

IND Requirements: 

• An IND must be in effect prior to the initiation of a clinical study of an investigational drug.
• Investigational use can mean a product not approved by the FDA for any use, or the use of an approved product in a way that is beyond its approved labeling (e.g., use, route, administration, etc.). 
• If a clinical trial is using an investigational drug to gather information about the products safety or efficacy, an IND may be required. 

IND Process:  

• Once determined an IND is required, a pre-IND meeting can be requested with the FDA.
• Finalized versions of all IND documents MUST be sent to the CRSO IND specialist, CRSO.FDAsupport@hsc.utah.edu, for review and approval prior to FDA submission. 
• Complete protocol, informed consent and information about the investigational product are required for submission of the IND.
• The FDA has 30 calendar days of receipt of IND submission to review. After 30 days, the sponsor- investigator may begin the study unless the FDA notifies the site otherwise.
• Emergency use and expanded access (compassionate use) IND options are available if urgent access is needed for a patient. 

CRSO IND specialist, Jonna Davis can assist Investigators through the process of preparing and submitting IND's. Contact CRSO.FDAsupport@hsc.utah.edu for assistance.