Nick Neri

This 3-part series is designed to outline the implications and processes for ensuring compliance with ICH E6 (R2) changes that are scheduled to go into effect late 2016. For an overview of the Addendum see 

, published on June 6, 2016 and for Part 2, ‘Six Steps to Compliance with ICH E6 Addendum,’ published June 13, 2016 click 

Part 3:  Driving Compliance through Technology: Act Now

	 	Leading voices in the biopharma industry are pushing changes in how risk based management (RBM) is approached in order to ensure the safety of patients and the integrity of trial data. The ICH E6 (R2) addendum is intended to deliver better quality, and to recognize the benefits of innovative methods like centralized, quality risk management (QRM) that should drive efficiencies and lower costs as well. 	 	In 2012, the non-profit, TransCelerate BioPharma launched the 

 to improve the quality and efficiency of RBM, and to describe a proactive approach for managing quality across the spectrum of clinical activities. This includes a framework for identifying risk indicators and performing consistent oversight of investigators throughout the trial lifecycle. 	 	Yet the industry as a whole has been slow to update their technology or processes to take advantage of the efficiency and regulatory benefits of a QRM approach. In many cases, sponsors are still relying on on-site monitors capturing data in spreadsheets to monitor risks manually, or attempting to use their electronic data capture system as a reporting platform for monitoring -- despite the fact that these tools don’t have that capability. As a result they are missing opportunities to cut time and cost while improving overall quality across the trial process -- a centralized approach to QRM has been shown to generate 

 â and potentially opening themselves up to quality and safety risks. 	 	Now that ICH has released the E6 (R2) 

 to GCP, they may also be exposing themselves to regulatory compliance issues when this addendum takes effect later this year. 	 	

Centralized Monitoring:  The Time is Now

	 	The addendum is expected to increase adoption of quality-by-design and QRM principles and methodologies in clinical development, while driving the use of innovative strategies and technologies for risk monitoring. It essentially mandates, harmonizes and clarifies what FDA and EMA have been suggesting in their guidances about the value of embracing a centralized, technology-driven approach to risk monitoring that begins in planning and continues through the life of the research. It further defines the scope of clinical trial oversight responsibilities, and the sponsor’s responsibility to establish a risk-based quality management system, ensuring the tools and methods used are “proportionate to the risks inherent in the trial and the importance of the information collected.” 	 	It also specifically cites “evolutions in technology and risk management processes” as the reasoning behind the change, and encourages industry stakeholders to seek out new tools and processes that will help them take advantage of these efficiencies. FDA added information to the document on conducting a centralized monitoring program and how to manage “significant noncompliance” to further establish unified standard across the trial site network.	 	This addendum should be a wake-up call for sponsors and CROs that it is time to change the way they think about and address quality risk management in the planning and implementation of their clinical trials. 	 	Nick Neri is the Insights Cloud Platform Manager for ERT

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This 3-part series provides insight into ensuring compliance with the ICH E6 (R2) Addendum to take effect later this year. Part 3 covers the value of embracing a centralized, technology driven approach to risk based monitoring.

Preparing for the ICH E6 (R2) Addendum: A 3-Part Series

This 3-part series is designed to outline the implications and processes for ensuring compliance with ICH E6 (R2) changes that are scheduled to go into effect late 2016.  For an overview of the Addendum see Part 1 of the series, published 

Part 2:  Six steps to compliance with ICH E6 (R2) Addendum

	 	The ICH’s new E6 (R2) addendum to Good Clinical Practice has the potential to change the way clinical monitoring and trial management are conducted by requiring adoption of centralized, quality risk management (QRM) throughout the trial lifecycle.	 	Trial sponsors and CROs recognize real, measurable benefits from taking a centralized, technology-based approach to risk management. These include reduced on-site monitoring costs, real time identification of risk trends across all trial sites and access to trial-wide views that enable them to capture best practices for future trials.	 	However, sponsors and CROs have been slow to adopt this centralized approach, likely because it requires some culture and technology transformation which can be difficult for some organizations to undertake. But the ICH addendum will soon be required, so companies need to start taking steps today to ensure compliance and to reap the time and cost savings benefits that come from a centralized technology-based approach to risk management. Here’s how:	

 Before making any changes, sponsors and CROs should assemble an in-house working group of GCP experts to study the new addendum, determine its full implications to their organizations and make decisions about how to adapt their technology and practices to meet the new requirements.

Develop technology and process gap analysis.

 Once the GCP team defines what compliance looks like for their organization, they should evaluate their current processes and technologies to determine if/where they fall short of the new requirements. For example, they may need to define a more formal risk identification process, create or acquire a library of risk identifiers, and/or replace manual spreadsheets with a more robust, technology-driven solution for assessing risks. This gap analysis will help them define a strategy for change and the steps needed to get there. 

 Most sponsors and CROs today rely on transactional study data drawn from numerous, diverse data capture systems like EDC, IVRS, Labs, etc. These data are often siloed and rely on unique codes and naming conventions. This lack of integration not only limits the sponsor’s visibility, but also makes it difficult to proactively identify and react to risks. To overcome these shortcomings, organizations should first identify where silos occur, then look for technology solutions that can remove the silos and integrate these systems’ data.  This will provide a single operational view that supports real-time risk monitoring across the entire trial site network.

 One of the biggest challenges companies will face is the culture transformation required to change the way risks are identified and managed in clinical research. To ease stakeholders into this new paradigm, organizations can roll out pilot projects with clearly defined metrics to demonstrate value and share case studies of other organizations that have already successfully made the switch. Studies show that a centralized approach reduces monitoring time and costs and often uncovers risks that on-site monitors miss. Demonstrating these benefits using real quantitative outcomes is the best way to engage stakeholders and increase their comfort with the change. 

 Regardless of whether a CRO is responsible for all clinical trial activities, the sponsor is still responsible for the quality, safety and efficacy of their processes and data. To ensure compliance with the addendum, sponsors should audit their CRO’s technology and QRM approach to determine if it meets ICH requirements and if not, how the CRO plans to move toward compliance. 

 The adoption of risk-based quality management has the potential to disrupt the industry and it has only just begun. To ensure compliance with the addendum and to achieve the greatest benefits, sponsors should look for opportunities to share learnings and participate in industry consortia, including TransCelerate BioPharma and the Clinical Trials Transformation Initiative, as they define standards and best practices for leveraging quality risk management strategies. 

Look for Part 3 of the series next week:  ‘Driving Compliance through Technology: Act Now’

	 	Nick Neri is the Insights Cloud Platform Manager for ERT

This 3-part series provides insight into ensuring compliance with the ICH E6 (R2) Addendum to take effect later this year. Part 2 covers steps that organizations can take today to begin adopting a centralized technology-based approach to risk management.

This 3-part series is designed to outline the implications and processes for ensuring compliance with ICH E6 (R2) changes that are scheduled to go into effect late 2016.	 	

Part 1:  Overview of the ICH E6 (R2) Addendum

	 	The International Conference on Harmonisation’s (ICH) addendum to the ICH E6 Guideline for Good Clinical Practice has many implications for clinical trial sponsors and contract research organizations (CROs).  The new 

E6 (R2) addendum to Good Clinical Practice

 has the potential to change the way clinical monitoring and trial management are conducted by requiring adoption of centralized, quality risk management (QRM) throughout the trial lifecycle.	 	One of ICH’s objectives with this addendum is to harmonize existing guidance from the US Food and Drug Administration (

) and others, which they believe are not currently aligned. The resulting lack of harmonization has left much room for interpretation, which can be confusing for organizations striving to meet regulatory requirements on a global scale. 	 	The addendum will require most biopharmaceutical companies and CROs to make significant changes to their risk culture and technology in order to be compliant, including the suggestion to implement a combination of on-site and centralized monitoring, and that the rationale behind each approach be documented. 	 	Centralized monitoring is critical for optimizing data quality in today’s complex clinical research landscape and, with the right tools in place, easily operationalized as sponsors and CROs strive to meet these important guidelines.	 	

	There are many advantages to implementing a centralized Quality Risk Management (QRM) system in addition to driving compliance with the new ICH standard. Centralization can also significantly cut the time and cost of clinical trials while helping to reduce risks. Yet most organizations are behind the curve when it comes to implementing the technology and processes needed to adhere to this new guideline change, and that may be putting them at risk.	 	This change is likely to go into effect by the end of 2016, which means organizations that haven’t started transforming their risk monitoring process are already falling behind. To catch up, biopharma stakeholders need to take the time now to read the addendum in full, define the impact it will have on the way they conduct trials, and devise a plan to adapt their technology and risk management practices so they can meet coming regulations while benefitting from a more centralized approach to managing clinical trial risk.	 	

Look for Part 2 of the series next week: ‘6 Steps to Complying with the ICH E6 (R2) Addendum’

This 3-part series provides insight into ensuring compliance with the ICH E6 (R2) Addendum to take effect later this year. Part 1 covers the addendums implications, objectives, requirements and advantages.