The resources which have been instrumental in the development of the Risk Index Model are provided below. Clinical trial management teams are encouraged to consult these documents and tools provided by the pharmaceutical industry, regulatory agencies and international bodies, to better understand how to implement Quality by Design (QbD), Centralized Monitoring and Risk-Based Monitoring (RBM) using XLSMetrics' solutions.
TransCelerate BioPharma Inc. was launched in 2012 as a non-profit organization to improve the health of people around the world by simplifying and enhancing the research and development of innovative new therapies. TransCelerate BioPharma’s mission is to collaborate across the global biopharmaceutical research and development community to identify, prioritize, design and facilitate implementation of solutions designed to drive the efficient, effective and high quality delivery of new medicines. TransCelerate BioPharma is comprised of the world’s leading biopharmaceutical companies, with the vision of simplifying and enhancing the research and development of innovative new therapies.
Risk Based Monitoring (RBM) Initiative
The Transcelerate BioPharma RBM Initiative was established in 2012 as one of the five initial goals created by TransCelerate to drive efficient and effective solutions into the R&D industry. By developing a model approach for risk-based monitoring of clinical trials, TransCelerate’s objective is to both enhance patient safety and ensure the quality of clinical data. The resource solutions generated by the Risk Based Monitoring Initiative could lead to improvement in data quality and patient safety for clinical trials and reduction in effort expended on low-value activities. In addition, adoption of the Initiative’s approach to Risk Based Monitoring could lead to cost reductions through more focused centralized monitoring activity and targeted on-site monitoring.
The Risk Assessment Categorization Tool (RACT) developed through the RBM initiative is a tool which can be used in conjunction with the risk (to quality) management strategy proposed by XLSMETRICS, namely in the selection of Key Risk Indicators (KRIs) which are to be monitored using the RI Calculator. Several resources pertaining to this initiative are available here:
Quality Management System (QMS) Initiative
Through partnerships with Health Authorities and other industry stakeholders, the QMS Initiative aims to explore ways to improve quality across the industry. The benefits of the Quality Management System Initiative include enhanced patient safety by improving quality, assuring data integrity, minimizing delays in clinical trials and bringing drugs to market more quickly.
In 2015, TransCelerate published a paper to provide an initial outline of a proposed conceptual framework for a clinical quality management system (QMS), an integrated system through which a sponsor organization can systematically plan and achieve clinical quality goals linked to their broader clinical and company strategic goals. The paper also explores how a clinical QMS framework can help alleviate issues related to trial inefficiencies that delay the process of bringing new, lifesaving medicines to patients.
This paper is highly pertinent to the objective of building quality into trials inherent to the model proposed by XLSMETRICS. The paper is available here:
Transcelerate QMS Initiative Concept Paper Vision and Outline
The Clinical Trial Transformation Initiative (CTTI) was established by the US Food and Drug Administration and Duke University in 2007. It is a public-private partnership to identify and promote practices that will increase the quality and efficiency of clinical trials. CTTI now comprises more than 60 organizations from across the clinical trial enterprise. Members include representatives of government agencies, industry representatives , patient advocacy groups, professional societies, investigator groups, academic institutions, and other interested parties. Of particular interest is CTTI's project on Quality by Design and Quality Risk Management applied to clinical trials. This project summary and toolkit are available here:
Quality by Design (QbD)
QbD is an approach that focuses effort on those “errors that matter” for the success of the clinical trial. By prospectively examining the objectives of a trial and defining factors critical to meeting these objectives, action can be taken to prevent important risks to these critical factors from negatively impacting outcomes. Understanding what data and processes underpin a successful trial is essential to subsequently identifying and managing important and likely risks to improve quality and outcomes for clinical trials.
XLSMETRICS's RI Model specificaly pertains to the Critical to Quality (CTQ) Factor of Data Monitoring and Management described in CTTI's QbD Project Principle Document available here:
CTTI QbD Project Principle Document
The Food and Drug Administration (FDA) has published a Guidance for industry oversight of clinical investigations - a risk-based approach to monitoring in 2013 to encourage the adoption of strategies which use a combination of monitoring strategies and activities in a RBM framework with an emphasis on Central Monitoring. This guidance can be found here:
FDA Guidance for Industry Oversight of Clinical Investigations – a Risk-Based Approach to Monitoring
The agency provides additional guidance to facilitate sponsors' implementation of risk-based monitoring in the following draft guidance published in March 2019.
RBM Questions and Answers Guidance for Industry
The European Medicines Agency (EMA) has published a Reflection paper on risk based quality management in clinical trials in 2013 to recommend a QbD approach for the implementation of a risk management process that includes risk assessment, risk control, risk review and reporting. This paper can be found here.
EMA Reflection paper on risk based quality management in clinical trials
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is unique in bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration. ICH's mission is to achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner. The ICH working groups have published two guidelines to steer the Clinical Research organization in the implementation of RBM and QbD strategies.
ICH GCP E6(R2)
The latest revision of the ICH guidelines due to be implemented by the end of 2016 has significant impact on any company looking to run clinical trials in the RBM and QbD frameworks. In order to properly use XLSMETRICS RI Model, clinical trial management teams must get acquainted with those guidelines which are available here:
ICH Quality Risk Management Q9
Risk management principles are effectively utilized in many areas of business and government including finance, insurance, occupational safety, publis health, pharmacovigilance, and by agencies regulating these industries. Today, the contribution that risk management has to offer to clinical trial enterprise has been recognized and organizations which are striving to implement quality systems instrumental in the deployment of QbD and RBM strategies should be familiar with the guidelines which are available here:
ICH Quality Risk Management Q9