The Demonstration of Improvement for Molecular Ovarian Cancer Testing (DEMO)

Project Title: The Demonstration of Improvement for Molecular Ovarian Cancer Testing (DEMO)

Project Lead & Pilot location Dr Elaine Leung, Pan-Birmingham Gynaecological Cancer Centre (PBGCC)

Dr Gabriel Funingana, CRUK Cambridge Centre

Inequality Criteria Minority Groups, Location

Objective Criteria Improve survival rates & access to care

Improve patient experience

The Demonstration of Improvement for Molecular Ovarian Cancer Testing (DEMO)

Full QI Project (10-15 minute read)

Overview:

The Demonstration of Improvement for Molecular Ovarian Cancer Testing (DEMO) aimed to improve the proportion of eligible women diagnosed with ovarian cancer successfully tested for relevant tumour and germline genetic variants in two vastly different regions in the United Kingdom (Birmingham and Cambridge).

Aims:

Improve Testing Rates: Increase the testing rate for ovarian cancer amongst eligible women in Birmingham and Cambridge, UK, for relevant somatic and germline mutations.

Enhance Information Accessibility: Provide multi-lingual, multi-media information for patients diagnosed with ovarian cancer.

Support Quality Improvement: Develop and implement new methods to identify areas for improvement in ovarian cancer care and testing.

Objectives:

Equity Enhancement: Using a co-production approach to enhance equity in ovarian cancer care in a diverse population.

Audit Pathway Analysis: Begin a prospective pathway analysis to identify areas for improvement.

Quality Improvement Methods: Test a new statistical method for evaluating genetic testing pathways.

Contribution to National Guidelines: Assist in updating national guidelines on genetic testing for ovarian cancer, disseminating best practices.

Expand Audit Infrastructure: Collaborate to expand the audit infrastructure beyond the initial sites in alignment with newly published quality performance indicators.

These aims and objectives collectively illustrate DEMO's comprehensive strategy to advance the diagnosis and care of ovarian cancer in the UK, with an emphasis on equity, innovation, and collaboration.

Background:

DEMO is tackling complex challenges related to ovarian cancer care in the UK, with an emphasis on addressing disparities in testing and systemic obstacles within healthcare.

Marked Variabilities

Language Barriers: In Birmingham, about 15% of women diagnosed with ovarian cancer are non-white. A significant proportion of patients required interpreting services (54% of this group spoke South Asian languages such as Punjabi, Urdu, and Bengali). This has contributed to an information gap and affected informed decision-making.

Previously Reported Barriers to Genetic Testing: Lower uptake in BAME groups has been noted due to a lack of awareness of inherited cancer risks, cultural attitudes, and absence of support for non-English-speaking women.

Lack of Clear Clinical Pathways: A significant gap exists within the multidisciplinary team regarding tumour testing, and there is a need for standardised pathways aligned with NHS England initiatives.

Effects of Treatment on Testing

Chemotherapy's Impact: More than 60% of women with ovarian cancer in the UK undergo chemotherapy before surgery. This treatment significantly reduces the proportion of tumour cells in a sample, further increasing test failure.

National Failure Rates: Over 34% of medical trusts in the UK have failure rates of more than 25% for tumour molecular tests, highlighting a serious issue with current testing practices.

Issues with Testing Procedures

Quality Assurance Lacking: There is an absence of rigorous quality assurance for biopsies, along with a shortage of specialist expertise in radiology and pathology to ensure that samples are fit for molecular testing.

Standardisation Required: The current lack of standardised biopsy pathways impacts the ability to conduct critical tests like deep whole-genome sequencing. There's a clear need for standardised processes to ensure quality biopsies.

Implications for Treatment and Patient Care

Funding Requirements: Quality tissue samples are needed for funding specific treatments like PARP inhibitors, which require the confirmation of faults in specific genes like BRCA1/2 or other measures of homologous recombination deficiency (HRD)

Improving Opportunities: Standardisation of biopsy pathways will not only enhance treatment standards but also broaden opportunities for women with advanced ovarian cancer to participate in novel clinical trials.

Summary: The challenges with obtaining biopsies for molecular testing in ovarian cancer are multifaceted in the UK. More than 60% of women undergo chemotherapy before surgery, impacting the sample quality and contributing to a national failure rate of over 34% in molecular tests.

The lack of quality assurance, standardisation in biopsy pathways, and the specific requirements for funding particular treatments further complicate the process. Addressing these issues is essential for improving treatment standards and expanding opportunities for advanced ovarian cancer care

Project design, planning and implementation

During our exploratory phase, we identified 3 main challenges we hoped to tackle:

• The lack of tailored information for a diverse population and patients with limited English proficiency (WP1)
• Obtaining biopsies that are of adequate quantity and quality required for molecular testing (WP2)
• The lack of clear clinical pathways that address the challenges of the often-complex diagnostic pathway involving both the secondary and tertiary care teams (WP3)

Patient Engagement and Involvement

Design and Strategising – The project began with consultations with an expert patient in Birmingham and the Cambridge patient advisory group, leading to key adjustments to the proposed work.

Identifying a Diverse Patient Advisory Group - Patients were selected with an emphasis on diversity, using recommendations from specialists and data linkage, including minority groups.

Co-Production Activities - Activities included pre-funding discussions, multiple meetings for reviewing drafts, a virtual “Thank You” event, and participation in consensus meetings. Feedback was used to finalise multimedia materials.

Next Steps - The future focus is on creating a sustainable co-production model with diverse patient and carer groups, aiming to improve equitable healthcare for ovarian cancer patients. Collaborations with charities, community groups and other stakeholders are being explored.

Data & Measures

Below is a concise section summarising the key outcomes:

Work Package 1 (WP1):

• Baseline Survey: Collected data on patients' understanding and experiences with genetic testing.
• Co-production Demographics Survey: Ensured diversity in the co-production group, collected data on technological skills, and previous genetic testing experience.
• Post-event Survey: Gathered qualitative feedback for improvement in future events.
• Social Media Analytics: Monitored the engagement levels of videos; metrics included number of views and locations.

Work Package 2 (WP2):

• Service Evaluation of Mainstreamed Testing: Analysed availability of germline and tumour tests results; identified variations across different sites.
• Linked Regional Cascade Testing Audit: Tracked parameters for those with germline pathological variants; captured ethnicity, referral proportions, and testing engagement.
• Prospective Audit of Genetic Testing Pathway: Used REDCap case report form to measure success rate of testing.
• MDT Engagement Audit: Measured discussion/documentation of genetic testing in MDT summaries.

Work Package 3 (WP3):

Webinar and Cambridge Ovarian Cancer Workshop Feedback: Collected qualitative feedback through educational webinars, assessed effectiveness, and identified areas for improvement.

Figures

WP1:

• Survey respondents: N=25
• Social media engagement: Views=ABC, Locations=DEF[EL(aGS1] [LW2]

WP2:

• Germline test results availability (from 2016-2021; Birmingham): 66%
• Cascade testing engagement (from 2016-2021; Birmingham): 93.5%

WP3:

• Webinar feedback (n=38):

- 36/38 agreed/strongly agreed the webinar was interesting

- 34/38 agreed/strongly agreed the webinar was useful and easily accessible

Results

Precis:

The DEMO project has undertaken a crucial exploration into the realm of genetic testing within the context of ovarian cancer, specifically within a standard NHS Trust. This work has led to the development of an data-driven approach that leverages data linkage of routinely collected clinical data and genetic test results to identify the test rates for patients diagnosed with ovarian cancer.

Notable findings include identifying variations in ethnicity recording and implementation rates of genetic testing across different hospitals, with non-white patients showing a higher chance of having pathological variants in the West Midlands. The study also uncovered a high uptake rate (100%) of genetic testing when offered and introduced a pilot genomic nurse role that engaged positively with genetic testing protocols. Furthermore, the exploration of a novel quality improvement technique and emphasis on professional development events related to genomic testing showcased the potential for enhancing clinical practice.

These insights not only underline the complexity within genetic testing in the NHS but also open avenues for improvements and innovations that could lead to personalised care and better outcomes for ovarian cancer patients. Future work by this and other teams could further clarify and address bottlenecks in the genetic testing pathway, guiding the design of educational events tailored for key multidisciplinary team members.

This following section will delve into the detailed results of the project, providing both qualitative and quantitative data that illustrate these critical findings and interventions:

Background:

Ethnicity:

• 18% of the cohort were non-white (9% Asian, 5% Black, 3% mixed/other, 1% Chinese), and 82% were White.
• Non-white patients were younger than white patients (61 years vs. 66 years) and had less favourable socioeconomic status (50% from the most deprived decile versus 20%).

Germline testing rates (2016-2021; Birmingham):

• Overall test rate: 66%
• By ethnicity: White: 69%, non-white: 75% (Asian: 82%, Black: 59%, mixed/other: 70%, Chinese: 100%)
• Implementation rate varied across the hospitals in the network; there was a significant difference between the most active and least active centres (84% vs. 22%).

Germline testing results (2016-2021; Birmingham):

• 14.2% of patients with a known genetic test result had a pathological variant or variant of unknown significance.
• Non-white patients had a higher chance of having a pathological variant (21%) or variant of unknown significance (5%).

Summary:

• The study identified significant variations in the test rates of germline genetic testing in ovarian cancer patients across different ethnicity groups and hospital centres.
• Non-white patients had a higher likelihood of pathological variants, highlighting the importance of genetic testing across diverse populations.
• The approach developed can be replicated in other NHS Trusts in the UK, aiding future large-scale studies and initiatives.

WP1: Post-event Survey for Co-production Events

• Themes for improvement:
• Communication of the results
• Addressing anxiety related to the wait time for results
• More diverse representation in patient volunteers

WP1 Summary:

Feedback from the co-production events and post-event surveys demonstrated that patients found value in engaging with the process, and there are areas for improvement that were identified.

WP2: Service Evaluation and Implementation of Novel Genomic Nurse Role:

• Pilot Intervention Outcome:
• Increased MDT engagement with genetic testing during the study period.
• Exploration of a novel QI technique (SPC) demonstrated its potential utility in the context of genetic testing.

WP2 Summary:

Brief intervention in the form of a genomic nurse role positively impacted the engagement of the MDT with genetic testing, an essential aspect for optimising patient care in the realm of ovarian cancer.

WP2: Service Evaluation of Mainstreamed Germline Genetic Testing at the PBGCC concise summary:

Hypothesis:

Differences in germline genetic testing rates by ethnicity in gynaecological cancers.
Methods:

Used various datasets to analyse patients diagnosed with ovarian cancer within the SWBH NHS Trust.
Results (n=546):

• Demographics: 25% from most deprived decile; non-white patients younger, more deprived.
• Testing: 66% were tested, improving from 51% in 2016 to 74.0% in 2021; significant difference between hospitals.

Ethnicity Insight:

No significant test rate difference by ethnicity, although there was a trend towards lower rate in black patients. Overall, two patients (6.5%) declined clinical genetics referral when a pathological variant was identified, both of them were non-white.

Summary:

Improved testing coverage over time, with some variations by hospital and a trend towards lower test rates in black patients within the PBGCC network.

WP2: MDT Engagement Audit:

Hypothesis:

The initiation of DEMO and the presence of a genomics nurse in MDT meetings are linked with increased engagement with genetic testing in ovarian cancer.

Methods:

Cohort study analysing MDT summaries of eligible cases for genetic testing in 2022.

Results:

• 134/263 (51%) eligible cases had genetic testing discussions in their MDT summaries.
• The discussion rate increased from 41% (January-June 2022) to 67% (July-December 2022), with significant peaks at key project milestones (p=0.037).
• A drop was noted in August 2022, coinciding with staff absences

Summary:

A significant increase in MDT engagement was observed in the second half of 2022, correlated with the presence of a genomic nurse. Future follow-up is needed to assess if this engagement will continue after the pilot ends.

Integration of whole-genome sequencing (WGS) in the NHS diagnostic pathway for high-grade ovarian cancer patients:

Hypothesis:

Integration of WGS is feasible and can improve the quality of fresh-frozen tumour samples for deep WGS.

Method:

WGS was performed on 19 patients' somatic and germline samples using Illumina chemistries, processed by Genomics England.

Results:

• Integration into routine care achieved after an initial 3-month run-in.
• Median time from consent to report was 48 days.
• A single all-inclusive test was preferred over multiple assays for better efficiency and comprehensiveness.
• Workflow on fresh-frosen tumor samples optimised and validated for precision and sensitivity.
• SPC chart displayed changes in cellularity over time, with wide control limits indicating need for a larger cohort. One instance of values outside the expected range suggests potential process issues.
• Extending the study to include a subgroup of patients who underwent diagnostic image-guided biopsy (IGB).

Summary:

The study demonstrated the feasibility of clinical WGS testing and the potential use of SPC charts to monitor cellularity as a quality marker for tumour samples and WGS success rate. The findings highlight the importance of an all-inclusive test, efficiency in reporting, and quality control measures in the WGS pathway.

WP3: Feedback after the Multidisciplinary Webinar:

Responses: 38 attendees

Positive Feedback:
• 95% found the webinar interesting.
• 89% found it useful and easily accessible.

Qualitative Feedback: Praise for multidisciplinary panel and content clarity; suggestions for more practical focus.

Patient Feedback: Positive reception, appreciated clear explanations.

Summary: Successful engagement with professionals and patients; recommendations for future focus on practical aspects of genomic testing.

Future Directions:

• Clarification of the bottleneck on the genetic testing pathway in different settings is essential.
• Design fit-for-purpose educational events tailored for key members of the multidisciplinary team.

Lessons learned

Practicalities of Running DEMO: Lessons Learned and Approaches in WP1, WP2, and WP3

Challenges and Solutions:

• Collaboration: Successful collaboration between leads, despite a tight timetable.
• Staffing Issues: Delays in job adverts and difficulties in hiring, mitigated by appointing an interim project manager and converting staff roles to full-time for short periods.
• Communication and Management: Complexities in secondment, line management structure, and high leave allowance led to communication challenges. Difficulties also arose in sharing documents with patient representatives, resolved by using Google Drive for non-confidential information.
• WP3 Impact: Decision to contribute to national guidance first added value to the project.

Approaches by Work Packages:

• WP1 - Diverse Co-production Group:
• Identified and engaged diverse patients, considering ethnicity, age, language, diagnosis stage.
• Ensured high-quality materials by involving professional communicators, animators, and regional clinical genetics teams.
• WP2 - Prospective Audit Pathway:
• Created infrastructure for scalability and future expansion.
• Developed a REDCap database, added new elements like MDT engagement audit and WGS pathway evaluation
• WP3 - National Guidance Contribution:
• Contributed and led the compilation of national consensus guideline documents.
• Focused on the delivery of the national consensus guideline [LW2] to allow wider adoption

Value of Patient Insights:

• Helped shape focus and evaluation of the project.
• Allowed discussion and consensus on the best multimedia sources, like animations.
• Exploited expertise amongst patient contributors and staff members in non-English languages for translation.
• Built a committed co-production group for further development.

Strengths of the Approach:

• Involved two different populations (size of population covered by PBGCC alone is more than the whole of East Anglia, while Cambridge has an established genetic testing infrastructure from its research portfolio), recognising site limitations.
• Focus on scalable infrastructure, independent of host NHS Trusts.
• National and international engagement to ensure outputs are incorporated into guidelines.
• Emphasis on patient involvement, co-production, diversity, and sustainability after the pilot

Limitations

Here's a summary of the key limitations encountered:

• Engagement with the Directorate’s Management: Lack of early identification and engagement with relevant teams, including finance and managerial staff, led to delays in finding appropriate paid staff. Correct signposting and early involvement of the Trust’s quality improvement team could have mitigated this issue.
• Challenges in Staffing: Delays in advertising paid roles, difficulties in communication with human resources, and struggles to identify staff with the right skills led to the hiring of a less-than-perfect fit for the project manager role. Future solutions might include alternative ways to fulfil this role or clear line management plans.
• Short Project Period: Ambitious goals within the limited timeframe were exacerbated by the pandemic and other external factors. Inefficient project management diverted attention from impact and legacy planning, and specific methods like statistical process control charts have not been tested.
• Engagement of Wider Networks: Late engagement with secondary sites and underutilisation of resources led to a lack of alignment and rapport among different clinical teams. Earlier and more consistent efforts could have mitigated these issues.
• Modification of WP1: Challenges in targeting a small proportion of patients for genetic testing and a lack of sensitive ways to identify those who declined testing limited the project's ability to explore specific aspects of BRCA testing in women. All of those who did not have germline testing and successfully approached stated that they could not recall being asked when approach. More extensive outreach at a regional level might have been a solution but was constrained by staff time and expertise.

Conclusion

A pivotal finding of our service evaluation was that a significant 1 in 4 patients within the PBGCC network did not have results from germline testing. This exposed variations in testing rates across different hospitals within the network, unveiling an area of concern. We engaged in a systematic outreach to this small subset of patients lacking genetic test results. Surprisingly, the majority could not remember being offered this vital testing.

Further exploration revealed a recurrent theme in our patient surveys: information overload. This insight underscores the need for a thoughtful approach to offering genetic testing, one that considers the patient's readiness and receptiveness. It suggests a nuanced strategy, possibly involving the provision of information at various stages of the patient's journey, to ensure that the importance of genetic testing is communicated effectively and that it resonates with those it is intended to help. Key aspects of DEMO that contributed to addressing systemic and regional health inequalities include:

Collaboration with Networks:

The project established connections with national guidelines and engaged with professional networks, regional cancer alliances, and genetic medicine alliance services. This collaboration allowed for the spread and promotion of the developed materials, demonstrating a commitment to wider community engagement.

Development of Multilingual Information: A diverse group of patients helped create multimedia, multilingual information. This made understanding the benefits and risks of genetic testing accessible to a broader population, addressing potential language barriers in the healthcare system.

Sustainable Models for Patient Engagement: The project's leaders are currently exploring sustainable ways to engage with a diverse group of patients. Collaborative efforts with charities and supportive organisations, along with initial funding for a pilot with Ovacome, showcase an innovative approach to long-term patient involvement.

Replicability and Learning Points: The preparation and training for genomic nurse roles, along with the availability of audit templates and job role descriptions, provide the groundwork for replicating the work elsewhere. By sharing these resources and learning points, the project has laid a foundation for others to apply this initiative, potentially reducing planning time and reaching more regions.

Data Management for Evaluation: The establishment of a data management system to collect anonymised data across multiple sites adds another layer to the ongoing evaluation of genetic testing pathways. This approach may further contribute to understanding and addressing disparities in healthcare access.

In conclusion, while the project faced challenges that impeded some progress, its achievements in collaboration, information development, sustainable engagement, and preparation for future replication indicate a substantial contribution to the overall program's aim. By focusing on these elements, DEMO has taken meaningful steps to tackle the systemic and regional health inequalities faced by women with ovarian cancer.

Outputs from project e.g. protocols, information for patients etc

We are considering using a separate box on the case study webpage rather than place within the main body text. Then we will link items listed below to the resource library.

Project Outputs:
Work Package Outputs

Work Package 1

Videos: Four videos produced in English and translated into Punjabi, Urdu, Bengali, Polish, and Romanian:

• What is genetic testing? (animation)
• What do the results mean? (animation)
• What happens if I agree to the tests? (Narrated video)
• What is an ultrasound-guided needle biopsy? (Narrated video with consultant radiologist)

Written Material: A patient information leaflet on genetic testing, translated into Arabic, Bengali, Punjabi, Urdu, Polish, Romanian, Simplified Chinese.

Data Gathering: Established baseline data on patient feedback regarding information and testing.

Work Package 2

Research and Evaluation: Results from a retrospective service evaluation covering mainstreamed germline genetic testing and linked review of cascade testing.

Audits: Prospective MDT summary audit on genetic testing incorporation.

Infrastructure: Establishment of data collection methods and prospective data collection.

Future Support: Obtained NCRI support for future calls of interest after a two-centre pilot.

Work Package 3

Guidance and Engagement: Participation in consensus guidance and further engagement with patient groups for feedback on genetic testing in ovarian cancer.

Webinar: A free multidisciplinary webinar on genetic testing, recorded for future dissemination.

Presentations: Presentations of early findings at national and international conferences.

Pilot Roles: Pilot of genomic nurse specialist and QI nurse specialist role, including job descriptions and training.