# Presentation: 506894

## 

Monitoring the Progress of Trials
 and the Safety of Participants

 Don Workman, PhD
               Victor Santana, MD		
    St. Jude Children’s Research Hospital

**Monitoring the Progress of Trials**
** ****and the Safety of Participants**
-  Don Workman, PhD
-                Victor Santana, MD
-     St. Jude Children’s Research Hospital
**	****	****	**

## A continuous ongoing review of the conduct of the trial

Shared responsibility

Research Team/Principal Investigator

Institutional Officials

Oversight Committees (IRB, DSMB)

- Shared responsibility
- Research Team/Principal Investigator
- Institutional Officials
- Oversight Committees (IRB, DSMB)

**Monitoring the Progress of Trials**
** ****and the Safety of Participants**

## Partnership in Research

**Investigator**

**IRB**

**Institutional**
**Officials**

**Participant**

## A Systematic Approach to the Problem

- Defining what needs to be monitored and reported
- Defining role of DSMB and role of IRB
- Developing infrastructure to report, evaluate and act upon safety concerns in a timely fashion

## Monitoring Elements as Summarized in the NCI Clinical Data Update System

**Patient-Specific Data**
-  	 –  demographics		–  treatment status (received therapy)
-   	–  date of entry			– off-therapy reason(s)
- subgroup on protocol
- eligibility			– performance status
- prior therapy		– disease code (diagnosis, SNOMED)
- treatment by course
- Course ID	    		– Start date
- Rx assignment (ph I)  	– BSA or weight
- dose of agent
- agent			– dose modification	 – total dose/course
- adverse even reporting
- type			– grade
- attribution			– reporting
- response
- evaluable			– best response at time of evaluation

## Monitoring 

| Type or Phase of Trial | Monitoring 
Interval | Reports to Subcommittee | Number of Patients to be Monitored |
| --- | --- | --- | --- |
| Phase I | Central Elements Continuously

Missing Data Reports Monthly | Quarterly | First 3 patients enrolled, plus 1 patient per dose level |
| Phase II | Eligibility and Consents Continuously

Central Elements Quarterly

Missing Data Reports Quarterly*

AEs Quarterly

Response coding semiannually, or at appropriate protocol time points | Semiannually, or 
as required in the protocol | First 2 patients enrolled, plus at least 10% of total patients accrued |

## Monitoring 

| Type or Phase of Trial | Monitoring 
Interval | Reports to Subcommittee | Number of Patients to be Monitored |
| --- | --- | --- | --- |
| Phase III | Eligibility and Consents Continuously

Central Elements Quarterly

Missing Data Reports Quarterly*

Response coding semiannually

Other primary objectives 
Annually
 | Semiannually, or 
as required in the protocol DSMP | First 2 patients enrolled, plus at least 10% of total patients accrued |
| ST JUDE holds
IND/IDE | Per study-specific monitoring plan | Per study phase | Per study phase, or study-specific monitoring plan |

## The Problem of AE/SAE Reporting and IRB Review

- Problems in reporting:
- Over-reporting (reporting of anticipated adverse events)
- Increased research in drugs and biologics
- Increased federal scrutiny—OHRP, FDA
- Saturation effects
- Lack of denominators in Safety Reports, lack of normative data for population under study

## The Problem of AE/SAE Reporting and IRB Review

- Problems in review:
- External events reports often sketchy summaries—no opportunity for questions/clarifications
- IRB is not DMC/DSMB
- IRB is not FDA with single IND file
- IRB needs to rely on local investigator to interpret the meaning of the events reported

## PI Reports & Categorizes Adverse Events

**Electronic Submission**

- IRB

- Office of RA

- Office of VP Clinical Trials

- External Reporting:
- OHRP
- CTEP
- NIH
- FDA
- RAC
- SPONSORS

- Internal Reporting

- Other Committees Institutional (DSMB, CPSRMC)

- Feedback

- Feedback

- Follow-up

## An Intranet-Based Solution for Collecting and Processing AE/SAE/UPIRSOs 

- Project Development
- 18 months from design to implementation
- Began with Implementation of a Form, designed like screen-shots to include checkboxes and fill-in the blanks
- Development of flow-diagram for Web-based Reporter
- Security versus Access issues
- Need for electronic “signature” other title 11 issues

## An Intranet-Based Solution for Collecting and Processing AE/SAE/UPIRSOs 

- Project Development
- Integration with existing databases
- Verifiable identities/access list
- Internal reports: subjects/medical record numbers
- Links to registered protocols
- Information stream to other PIs
- External reports: radio buttons for selecting protocol(s) for reporting of events (sometimes multiple studies on single safety report)
- E-mail notification to PIs

## An Intranet-Based Solution for Collecting and Processing AE/SAE/UPIRSOs 

- Functional Outcomes
- Real-time IRB reporting: time stamping
- Forced choice, smart forms, no incomplete submissions
- Ease of access—any system signed onto intranet
- Ability to generate single-incident reports
- Ability to generate reports entered in specified time period

## An Intranet-Based Solution for Collecting and Processing AE/SAE/UPIRSOs 

- Functional Outcomes
- Quicker reporting times
- Ability of IRB Office to generate reports based on protocols, type of events, across subjects
- Able to generate internal denominators
- Use of standardized NCI toxicity tables
- Able to record IRB actions, and updates from Investigators onto previous reports

## An Intranet-Based Solution for Collecting and Processing AE/SAE/UPIRSOs 

- Process Improvements
- More timely reporting—able to demonstrate overall compliance
- Better communication between investigators and IRB
- Able to manipulate information into reports
- Improved information summary presentation for reviewers
- Easy access to history of events on any protocol

## An Intranet-Based Solution for Collecting and Processing AE/SAE/UPIRSOs 

- Process Improvements
- No need for generating additional correspondence
- PI can generate time-stamped “receipt” by IRB and determinations from the Committee
- Requires PI input on judgments re. Seriousness, relationship (related/not related), and  expected/unexpected
- Requires PI judgments regarding need for revision/amendment to consent/protocol

## 

DEMONSTRATION

**DEMONSTRATION**

## Slide 18

## Slide 19

## Slide 20

## Slide 21

## Slide 22

## Slide 23

## Slide 24

## Slide 25

## Dr Teddy Bear

**Dr Teddy Bear**

## Slide 27

## Slide 28

## Conclusions

- Technology can be used to improve process for collection and review of information regarding adverse events
- Web-based applications can facilitate cross-talk between various databases
- Well-designed systems may allow for a single report in an inpatient hospital to generate incident reports, ADR reports, medwatch reports, and AE/Safety reports

## Acknowledgments

- Don Workman, Ph.D., IRB Administrator (2003)
- Donna Hogan, IRB Office, CIP
- Mickey Weeks, Clinical Informatics
- Donald Sanderlin, Clinical Informatics
- Victor Santana, M.D