Major Industry Groups Offer Feedback on ICH’s E6(R3) Guidelines
Four major industry groups shared their thoughts on the International Council for Harmonisation’s E6(R3) draft GCP guidelines, commenting on stakeholder engagement, diversity and service provider evaluations and pointing out areas that need greater detail.
The FDA’s call for feedback, which ended Sept. 5, netted comments from 18 stakeholders at time of publication, including the WCG Avoca Quality Consortium (AQC), the Society for Clinical Research Sites (SCRS), the Association of Clinical Research Organizations (ACRO) and the CDISC Trial Master File (TMF) Reference Model Community.
SCRS’ 18 pages of comments offer suggestions for clarifying terms, concepts and wording and improving processes, accountability and industry collaboration. For example, it raised a number of questions around the draft’s GCP principle 1.4, which says participant selection processes “should be representative of the anticipated population who is likely to use the medicinal product in future clinical practice to allow for generalizing the results across the broader population.”
SCRS believes further clarification on diversity is still needed, such as how it should be measured and what the expectations are for global programs in which diversity may become a more complicated endeavor. “As written, there is lack of a pragmatic description that contributes to the negative effects that the politicization of the issue is having ... this would be difficult to do on a trial basis and should be part of an overall development plan, and thus eliminated as an individual trial requirement,” SCRS said.
ACRO, which eagerly awaits the opportunity to see what the not-yet-released Annex 2 of the guideline will recommend for decentralized trials (DCT), applauded the guideline’s emphasis on stakeholder engagement but believes this area can be bolstered. In its four pages of feedback, the organization advised that stakeholder engagement should start as soon as possible and carry on throughout the planning process and encouraged ICH to further stress the important role diversity plays in ensuring trial outcomes are relevant to a broader group of patients.
ACRO also believes that the guideline’s language on sponsor oversight of providers “could inadvertently be interpreted in a way that constrains the quality management role of the service provider,” and suggested wording to correct this.
AQC’s comments featured crossfunctional feedback on behalf of its members, representing sites, sponsors, CROs and service providers. In addition to recommendations for additional clarity, AQC emphasized training opportunities that its members feel will help with implementation of the guideline, responding to ICH’s request for training recommendations from stakeholders to inform detailed training resources it intends to develop.
AQC’s training-related comments focused on significant revisions, including the newly added section on data governance, the Appendix C essential records section and the investigator section that has seen considerable broadening of investigator responsibilities.
“We anticipate that robust training will strengthen understanding for individual stakeholders as well as ensure consistency across all clinical trial stakeholders,” Karen Harvey, senior director of Avoca, a WCG Company, told CenterWatch Weekly.
For example, AQC believes there’s a training opportunity for the continuing risk-based reviews the guideline directs IRBs and institutional ethics committees (IEC) to conduct for each ongoing trial. Specifically, the consortium has asked for examples of risk levels and the documentation expected for these procedures and risk assessments “to ensure understanding and consistency across IRBs [and] IECs.”
AQC also commented on the guideline’s recommendation that sponsors review whether systems deployed by investigators and institutions, such as electronic health records, are fit-for-purpose for trials, noting a lack of details on how these assessments should be carried out and documented. On this, the consortium recommended that ICH develop training materials that share use cases.
In addition, AQC noted a lack of guidance for investigators regarding the assessment of service providers based on information given by the sponsor. This too is an area that would benefit from training materials, the consortium said in its feedback.
“Language should be added to provide guidance for investigators on the assessment of service providers, what information should be provided by the sponsor and documentation of decisions.” Avoca wrote. “Use cases would be helpful to highlight the collaboration needed by sponsors and investigators to support appropriate qualification activities.”
CDISC’s feedback stuck to one area of the guideline: its list of essential and “potential essential” records that are to be part of a TMF. In its current state, CDISC believes this list lacks many record types and does not provide a full picture of trial conduct and data quality.
“We strongly believe that this will cause confusion in an industry where we have established a de facto standard for the contents of a TMF,” the group noted, requesting the list be removed entirely and attention directed toward the guideline’s Essentiality of Trial Records section, as well as its own TMF Reference Model.
Read all the comments here.