New Survey Measures the Pulse of RBM & ICH-E6 (R2) Adoption in the Clinical Trials Industry

From digital conversations to live panel discussions, the topic of risk-based monitoring (RBM) often dominates discourse in the clinical trials industry. The popularity of the topic, however, obscures the inconsistencies surrounding the industry’s adoption and implementation of risk-based approaches to monitoring. A new survey from eClinical Forum, in partnership with OmniComm Systems Inc., highlights the gaps in the conversation, including the sharp divergence in RBM adoption between larger organizations and other institutions.

Background about RBM and ICH-E6(R2)

Regulatory endorsement in the form of guidance and reflection papers generated the impetus to adopt risk-based approaches to monitoring^1,2. A position paper from TransCelerate Biopharma Inc., (a not-for-profit consortium of organizations in the Life Sciences space) provided the much-needed guidance to operationalize risk-based approaches to monitoring^3,4,5. Other industry forums, including eClinical Forum, have promoted best practices to enable risk based approaches to monitoring⁶.

In the last couple of years, formal amendment of E6 section of ICH (International Conference for Harmonization) - pertaining to Good Clinical Practices (GCP) and now commonly termed as ICH-E6(R2) - has taken center stage for clinical operations. The formalization of ICH-E6(R2) in 2016 and subsequent adoption of the same by regulatory agencies such as EMA and Health Canada^7,8 established a regulatory expectation on organizations to comply, thus setting an inflection point for organizations to transition to a new and holistic mechanism of functioning.

Over the last two years, the industry has seen increased awareness of risk-based approaches to monitoring. It is encouraging that large sponsors and contract research organizations (CROs) have streamlined processes and offered risk-based approaches to monitoring as the primary model of delivery for outsourced studies. This approach or model is still developing, and organizations have utilized a variety of interpretations and approaches to achieve the same outcome. The industry has yet to adopt a standard delivery model for RBM.

How extensively has the industry implemented RBM? eClinical Forum, a non-commercial, global discussion and action forum, and OmniComm Systems, a leading global provider of clinical data management technology, sought insights that organizations could utilize to shape operational and business strategy in the changing paradigm.

Survey results indicate that larger organizations have either developed mature processes or are well onto the path of carving out a delivery model that accommodates ICH-E6(R2) requirements. In contrast, small and medium-sized organizations are only beginning to recognize the requirements of ICH-E6(R2) compliance.

Survey methodology

The survey was launched in June 2018 through eClinical Forum member channels and through an email survey campaign to professional contacts in the industry. The survey was conducted in a neutral manner irrespective of size, type or geographical basis. Respondents were anonymous. More than 3,000 emails across 3,397 organizations were sent, and 211 respondents participated in the survey.

https://www.omnicomm.com/blog/omnicomm-and-eclinical-forum-release-survey-results-on-ich-e6r2-and-rbm-implementation

Highlights

• Organizational Representation of Respondents: Representatives from sponsors and CROs (pharma, biotech and medical device organizations) accounted for the highest number (about 75%) of respondents. The remaining respondents represented academic research (11%) and other stakeholders (13%). The “Other” category included consultants, SMOs and eClinical vendors.

• Size of Respondent’s Organization: A majority of respondents (about 58%) constituted non-large organizations (small and mid-size organizations). About 42% of respondents represented larger organizations. The respondent distribution across different sizes of small/midsize organizations was equitable.

• Use of RBM: A majority of the respondents reported that their organization is currently using RBM (64%) and nearly one-third (29%) noted that their organization is not currently using RBM. A small percentage (6%) of respondents were not sure if their organization was using RBM. Further analysis of the responses reveals that organizations on the larger end of the spectrum were more likely to have applied RBM in their organizations.

• Geographical differences: Approximately, 76% of respondents from Europe and the Middle-East region reported that their organizations were implementing RBM, and that response was uniform across large and non-large organizations. The Americas region had about 64% of organizations applying RBM. Organizations headquartered in the Asia-Pacific region had about 52% of organizations applying RBM.

• Barriers: From this survey, lack of organizational readiness, especially from a process perspective seems to be the biggest challenge. Large organizations have made significant progress in developing processes pertaining to ICH-E6(R2) implementation. Some of them must be maturing in their processes. Non-large sized organizations are beginning to evolve.

• Targeted SDV: The industry will continue to use targeted SDV. Organizations that have not moved away from 100% SDV on all studies might want to reexamine alternate SDV models, especially TSDV. Also, processes that link risk monitoring to TSDV should become an essential strategy for execution.

• Technology enablement: Data visualization is one of the most preferred formats for data review. This is relevant in the context when multi-dimensional data needs to be used for correlation and review. Though data exports are also being used, scalability can become a pain point for the industry when ICH-E6(R2) becomes the new normal. One needs to view the expected challenges when data from more than one system is going to be used, and when trends and patterns need to be observed. RBM tools that can accommodate off-the-shelf or home-grown statistical techniques to be embedded will be an added advantage.

Summary and conclusion:

It can be inferred from the survey that the adoption of those principles has been mixed in the industry. Large organizations are well on the path to implementation. Many of those organizations seem to have mature processes to implement risk planning and monitoring. Small and mid-size organizations (grouped as non-large organizations) are primarily in the early stages of implementation. Those organizations are beginning to accept the requirement to transform their operational processes and methodology.

Key findings from the survey responses are as follows:

In conclusion, small and mid-sized organizations must recognize that pursuing global markets for new drug approvals is increasingly at risk, especially in Europe and Canada in short term, given the requirements to adhere to ICH-GCP(R2) requirements.

The gap in value differentiation between small/mid-size CROs and large CROs have significantly widened in recent years – from a scalable regulatory and quality compliance perspective, given the ICH-E6(R2) requirements. It would serve the small and mid-size CROs well to expedite remedial interventions at a process, people and technology level to continue being relevant in the global clinical research landscape.

References:

1. AUG-2013: FDA Guidance: Oversight of Clinical Investigations - A Risk-Based Approach to Monitoring
2. NOV-2013: EMA Reflection Paper: Risk-based quality management in clinical trials
3. 2013 position paper: Risk-based monitoring methodology
4. TransCelerate Risk Assessment Categorization Tool (RACT) & Protocol-level risks and Integrated Quality Risk Management Plan (IQRMP) ((https://www.transceleratebiopharmainc.com/assets/rbm-assets/ )
5. TransCelerate Updates and FAQs from 2013 to 2015 (https://www.transceleratebiopharmainc.com/assets/rbm-assets/ ):
6. RISK-BASED MONITORING UPDATE - VOLUME 1
7. RISK-BASED MONITORING UPDATE - VOLUME 2
8. RISK-BASED MONITORING UPDATE - VOLUME 3
9. RISK-BASED MONITORING UPDATE - VOLUME 4
10. eClinical Forum: Risk-Based Approaches - Best practices for ensuring clinical data quality (Sept, 2013)
11. Europe Medicines Agency: ICH-E6(R2) Good Clinical Practice; Revision 2, adopted guideline; Published: 15/12/2016, effective: 14/06/2017
12. Notice - Interim Implementation of International Council for Harmonisation (ICH) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) – May 11, 2018. Guidance Document: Good Clinical Practice: Integrated Addendum to E6(R1)ICH Topic E6(R2); Date adopted: 2016/11/09, effective date: 2017/05/25

Abby Abraham is the vice president of Data Analytics and Risk-Based Monitoring at OmniComm Systems, Inc.

The author acknowledges Ken Light, executive vice president, Corporate Strategy, and Meredith Bell, clinical solutions consultant, both of OmniComm Systems, Inc., for their contributions to the design and execution of the survey featured in this article. The author also acknowledges the editorial assistance of Sharon Harvey Rosenberg, scientific journalist at OmniComm.