Clinical Trial Approval (CTA) Scheme - Targeted consultation with Human Research Ethics Committees (HREC)

We asked Human Research Ethic Committees (HRECs) for feedback on the Clinical Trial Approval (CTA) scheme. We sought feedback on:

• HREC’s approach to recommending the CTA pathway
• HREC target timelines and processes
• the CTA process and scope
• engagement and collaboration with the TGA

We received seventeen (17) responses from HRECs, with various experience with trials that have been submitted under the CTA scheme.

Key response themes include:

• Confusion about
  • the TGA CTA process and evaluation scope
  • whether TGA approval is required prior to HREC ethics approval
  • who is responsible for recommending the CTA pathway for certain therapeutic goods
• Lack of collaboration and communication between the TGA and HRECs

HREC’s approach to recommending the CTA pathway

We received mixed feedback on how HRECs approach recommending the CTA pathway. When determining whether to recommend the CTA pathway to a sponsor, HRECs consider several risk-based factors, including:

• HREC expertise required for thorough scientific and ethical review
• TGA advice to the sponsor
• trial design, including patient safety, privacy, and good clinical practice
• trial documentation, including trial protocol and investigator’s brochure
• qualification of researchers
• international approvals

Multiple respondents mentioned that recommending the CTA pathway is rare or they have no experience. Several reasons were mentioned, including: 

• the sponsors have already sought TGA advice or applied for CTA approval
• high-risk and/or first-in-human trials may be reviewed by different specialised HRECs

HREC target timelines and processes

We received feedback that helps us understand the different timelines and processes for HRECs. Review timelines for each HREC vary but most hold a monthly committee meeting. Most HRECs review trials within 30 to 60 calendar days and submission deadlines occur 2-3 weeks prior to the monthly meeting.

Most HRECs have the same process for applications going through the CTN or CTA pathway, however a few HRECs said that submission may be delayed/review timelines may differ if TGA approval for a CTA has not been received.

The CTA scope and process

Feedback identified the following issues:

• lack of clarity around the CTA process, including who is responsible for recommending the CTA pathway
• lack of clarity on the criteria that the TGA uses to evaluate CTAs
• confusion on the order of the TGA and HREC approvals – for example, we received feedback that since the TGA does not consider ethical aspects of the trial, the TGA’s approval should be conditional until HREC approval

Many HRECs noted that it was highly likely that some aspects of their review would be duplicative of the TGA’s evaluation and that it would be difficult to reduce this. For example, multiple respondents mentioned that both reviews would cover the protocol and investigator’s brochure. However, this duplication was seen as necessary as the focus of the review differs. Conversely, a few HRECs said no duplication of documentation would be required.

Engagement and collaboration with the TGA

HRECs would appreciate greater collaboration, partnership and information sharing between themselves and the TGA – for trials under both the CTA and Clinical Trial Notification (CTN) schemes. Some HRECs engage semi-regularly with the TGA especially if a study requires a CTA, and these interactions are highly valued.

HRECs noted that being unsure of who to contact for advice and difficulty finding specific information are barriers to engaging with the TGA. However, they also noted recently that the TGA responses to enquiries have improved, and the increasing frequency of webinars are helpful.

Suggestions for improved engagement and education opportunities included:

• earlier joint discussions with sponsors and HRECs when a CTA is intended to be submitted
• informal joint problem-solving discussions on emerging issues, uncertainties and challenges faced by HRECs  
• broadening webinar topic areas to educate HRECs on issues that should be considered when reviewing trials with novel/high-risk therapies, and to include de-identified case studies.
• education for HRECs to be able to identify GCP deficiencies in clinical trial/protocol design

We are incorporating the feedback into the next phases of the CTA scheme review.  

Next steps

• we will be undertaking further rounds of consultation with wider groups of stakeholders.
• we have published a webpage “Review of the Clinical Trials Approval (CTA) scheme” that will contain updates on the review and outlines the TGA’s current CTA process.
• we are investigating further opportunities for collaboration between HRECs and the TGA.
• we are incorporating the feedback from HRECs when considering educational opportunities. HRECs can contact gcp.inspection@health.gov.au for GCP compliance related questions