Section 5

The Next Frontier of RBM

Category 1: Management of Technology Solutions

Category 2: Integrating Change Management

Category 3: Managing Guidance and Requirements from Health Authorities

Category 4: Identifying the Right Metrics

GLOSSARY: Key Terms Defined

GLOSSARY: Key Terms Defined

Centralized Monitoring

An evaluation carried out by sponsor personnel or representatives such as a data manager, statistician or monitor

Critical Data

Data that are critical to the reliability of the study findings, specifically those data that support primary and key secondary endpoints, as well as data that are related to subject safety and rights

Critical Processes

Processes that are critical to the reliability of the study findings, and those related to ensuring subject safety and rights

Integrated Quality and Risk Management Plan (IQRMP)

A tailored and integrated plan for a specific clinical trial that will:
  • Include the clinical and medical risks identified at the program level
  • Define the actions that each function will take to proactively identify, assess, and manage risk throughout the life of a clinical trial
  • Define the Critical Data identified by cross functional representatives
  • Align associated quality management plans (including the Monitoring Plan) across identified risks and defined Critical Data and Processes to ensure cross-functional teams focus on the risks that are most important to subject safety, data quality and regulatory compliance
  • Describe the process that each function will follow to review and revise the IQRMP throughout the life of the clinical trial

Monitors

The individuals responsible for enacting the plan and identifying risks

Off-site Monitoring

Monitoring activities that occur away from the study site location, such as at a monitor’s home or in a sponsor representative’s office. This is also commonly known as remote monitoring

On-site Monitoring

An in-person evaluation carried out by sponsor personnel or representative(s) at the site(s) at which the clinical investigation is being conducted

Overall Risk Level

An estimate of the level of risk described as high/medium/low that guides the application of a baseline monitoring approach

Quality

Quality in clinical trials is defined as the absence of errors that matter, which are errors that have a meaningful impact on patient safety or interpretation of study results1

Quality by Design (QbD)

Systematically building quality into a clinical trial design to ensure that processes are focused on what is critical, and are performed in a way that mitigates errors that would have the greatest impact on subject safety and data quality

Quality Data

The US Food and Drug Administration (FDA) defines quality data as data that are fit-for-purpose and sufficiently accurate to support regulatory decisions and sponsor claims about a product and its labeling 2

Quality Risk Management

According to the US FDA, quality risk management is a systematic process for the assessment, control, communication and review of risk to the quality of the drug product across the product lifecycle 3

Risk

Uncertainty in achieving your objective; according to the new International Organization for Standardization (ISO) standard – the potential that something could happen4

Risk Assessment

The process by which potential risks that could affect subject safety, data quality or regulatory compliance are examined. Includes categories such as study phase and subject population

Risk-Based Monitoring

An adaptive approach to clinical trial monitoring that directs monitoring focus and activities to the evolving areas of greatest need which have the most potential to impact subject safety and data quality

Risk Indicators

Metrics used to monitor identified risk exposures over time

Source Data Review (SDR)

A distinction exists between Source Data Verification (SDV) and Source Data Review (SDR), in that SDV is the comparison of source data against the CRF data, and SDR is not a comparison of source data against CRF data

SDR involves:

  • Review of source documentation to check quality of source
  • Review of protocol compliance
  • Ensuring that the Critical Processes and source documentation are adequate
  • Ascertaining Investigator involvement and appropriate delegation
  • Assessing compliance to other areas (e.g. GCPs)

SDR is necessary to evaluate areas that do not have an associated data field in the CRF or a system available for more timely remote review

Source Data Verification (SDV)

Commonly known as “transcription checking,” this is the process by which data within the case report forms (CRF) or other data collection systems are compared to the original source of information (and vice versa) to confirm that the data were transcribed accurately – that the data from the source matches data in the CRF

Thresholds

The level, point, or value associated with a Risk Indicator that will trigger an action such as increased data scrutiny or site follow-up

 

1. Meeker-O’Connell. Update on clinical trials transformation initiative (CTTI) quality-by-design project. DIA Quality Risk Management Conference 2012, Philadelphia, PA.
2. US FDA
3. US FDA, Guidance for Industry – Quality Risk Management
4. ISO Standards, ISO 31000 – Risk Management

Section 6: RBM Toolbox

Initiative Resources