Improving Trial Design and Delivery Through Early PPIE

The ATTEST Case Study

Context

The ATTEST study is a first-in-human clinical trial evaluating ATTR-01, an oncolytic genetically modified virus developed by Accession Therapeutics. The study is recruiting in the UK and Europe. The Patient and Public Involvement and Engagement (PPIE) activities were delivered in collaboration with the Cardiff Experimental Cancer Medicine Centre (ECMC) Patient and Public Involvement (PPI) team.

As the trial involves participants with stage 4 cancer, it was important to understand participants’ priorities, concerns, and views on the study design, particularly in light of the complex practical, emotional, and clinical factors that could influence treatment decisions in this group. PPIE is strongly encouraged by regulators, ethics committee and funders, and is a key component of clinical trial approval. PPIE was therefore embedded at an early stage of clinical development to assess the acceptability of trial procedures and to help ensure that the study design and participant-facing materials were aligned with the needs and concerns of the participant population.

PPIE Activities

The team implemented a PPIE strategy in line with the UK Standards for Public Involvement.

The work featured a focus group made up of two complementary subgroups. One subgroup consisted of experienced strategic PPIE contributors, who reviewed complex study materials including the full protocol and participant information and consent sheet, and contributed to discussions relevant to ethical approval. Following this initial review, key areas for further discussion were identified and used to plan a wider subgroup of lay patient members and carers with lived experience relevant to the study’s specific disease areas, recruited through the ECMC PPI team and national ECMC network. This structure enabled the team to combine strategic PPIE input and activity design with direct, unbiased insights into participant priorities, concerns, and practical burden.

The focus group informed several aspects of the study’s development. Working collaboratively with the clinical team, PPIE contributors helped shorten, reorganise, and improve the accessibility of the content used throughout the participant information sheet, lay summary, and other study documents, including the protocol. Specific examples raised by contributors included the view that the term “study” felt less daunting than “trial”, and that the ordering of risk-related or other information that might be perceived negatively could impact confidence in participation. Together, these insights enabled the team to adopt language that was more acceptable to participants and helped shape how patients perceived the information presented to them. In addition, the team co-developed lay-friendly infographics to explain the complex science underpinning the investigational Advanced Therapy Medicinal Product (ATMP). These materials made the information more accessible and supported informed decision-making.

The focus group further challenged assumptions made by the clinical team about what level of burden cancer study participants would and would not be willing to accept. In many cases, participants were more open than expected to undergoing additional clinical procedures, which, when viewed in the context of high baseline test burden for cancer patients, were of less concern. This helped the developer avoid unnecessary protocol changes that might otherwise have reduced the study’s scientific or operational value.

Finally, the experienced PPIE subgroup supported the commercial team in preparing for the Research Ethics Committee (REC) review meetings, and attended the review to demonstrate that the study had been shaped in response to patient perspectives and to address any PPIE questions during the session.

The ATTEST study provided a strong example of how early incorporation of PPIE improved study planning, strengthened trust and collaboration, and delivered tangible benefits for the developer. It showed that PPIE was not only good practice but also a practical tool for enhancing study quality, reducing development risk, and supporting more efficient clinical progress, thereby helping to accelerate clinical development.

Commercial benefits of PPIE

Better trial design and more efficient delivery: PPIE helped to balance clinical priorities with patients’ practical needs, making the study more feasible, inclusive, and aligned with patient-centred outcomes. Improvements to patient-facing materials supported participants’ understanding, engagement, recruitment, and retention, while also helping to build trust in a well-considered study design. Overall, PPIE contributed to more efficient trial delivery, resulting in a shorter development pathway and potential cost savings. PPIE-supported inclusion of informative tests and scientific endpoints also led to a broader data package for onward commercial utility.

Stronger regulatory review: PPIE strengthened ethics submissions by demonstrating that the study had been shaped by the target population. Support from experienced PPIE contributors at REC meetings helped address patient-related concerns early, reducing the likelihood of ethics queries, revisions, and avoidable delays.

Financial and reputational value: By improving trial design, submission quality, supporting recruitment and retention, and reducing the risk of delays, PPIE lowered both development costs and reputational risk. Early input helped identify barriers to participation while they were still relatively inexpensive to address. Meaningful patient involvement also strengthened the company’s credibility with regulators and patient communities.

Learn more about the commercial benefits of PPIE in PPIE Beyond Ethics: A Business Case for ATMP Developers

Key Learning

Implementing PPIE early: PPIE was most effective when introduced before the study design was finalised, as this improved study feasibility and reduced the possibility of costly amendments later in development.

Involving contributors who match the target population: Patients and carers with experience closely matched that of the target population were best placed to identify specific barriers to participation, assess acceptability, and highlight what mattered most to participants when making treatment decisions.

Partner with UK PPIE teams to deliver high quality PPIE work: Finding the right patient groups and designing effective, impactful PPIE activities can be challenging. However, the UK has developed strong PPIE networks to support commercial partners through this process.

Using different contributors for different purposes: A combined model offered particular value -- experienced PPIE contributors supported document review, regulatory processes, and helped to plan PPIE activities, while lay contributors with relevant lived experience provided key insights into participant’s informational needs, practical burdens, and the overall acceptability of the study.

Keeping information accessible and relevant: The wording, format, and order of presentation strongly influenced how the study was perceived. Clear language and visual tools, such as infographics, helped explain the complex science behind ATMPs in a more accessible way. Improving participant’s understanding not only supported their informed decision-making, but also enhanced the overall quality and acceptability of the study and therefore supporting recruitment objectives.

Drawing on PPIE expertise to support meaningful involvement: PPIE expertise helped patients and carers understand the context of clinical research, as well as the purpose and value of their contribution. It also provided a supportive framework for discussions that could potentially evoke difficult personal experiences.

Infographic Summary

This infographic can be downloaded from the attachments section below.

Acknowledgments

Author

Dr Hsin-Yu Kuo, EuroGCT Project Manager – Research Information and Networks.

Reviewed by

Emily Merrell, Director, ATTC network Coordination

Hannah Ekbatani, Programme Manager, ATTC network

Julia DeCesare, Senior Director, Clinical Operations, Accession Therapeutics Ltd.

Dr Joanna Zabkiewicz, Translational and PPI Academic Lead, Cardiff Experimental Cancer Medicine Centre (Cardiff ECMC)

Julie Hepburn, Lay Lead, Cardiff Experimental Cancer Medicine Centre (Cardiff ECMC)

Pia Donaldson, Clinical Study Manager, Clinical Operations, Accession Therapeutics Ltd.

Sarah Kernaghan, Clinical Study Manager, Clinical Operations, Accession Therapeutics Ltd.

Prof Hardev Pandha, Medical Director, Accession Therapeutics Ltd.

Dr David Krige, Chief Development Officer, Accession Therapeutics Ltd.

This case study was developed on the basis of interviews with Julia DeCesare, Senior Director, Clinical Operations, Accession Therapeutics Ltd.; Dr Joanna Zabkiewicz, Translational and PPI Academic Lead, Cardiff Experimental Cancer Medicine Centre (Cardiff ECMC); Julie Hepburn, Lay Lead, Cardiff Experimental Cancer Medicine Centre (Cardiff ECMC); and Angela Harris, PPI Officer, Cardiff Experimental Cancer Medicine Centre (Cardiff ECMC). Additional support was provided by Dr Philippa Pristerà, co-founder of PhiZ & Co., and James Ellaway, Data Lead, Cardiff Experimental Cancer Medicine Centre (Cardiff ECMC).

We thank all contributors for their invaluable insights and support in the development of this case study.