An ethical framework for combining routine service delivery with research

Dr van der Merwe is a Medical scientist and HPCSA-registered Genetic counsellor with a history of
working in both the academic and private sectors. She currently provides research and clinical
consultation to Gknowmix and Cape Peninsula University of Technology. She obtained a PhD degree
(Pathology) from Stellenbosch University in 2016, under the supervision of Professor Maritha Kotze
who founded Gknowmix’s pathology-supported genetic testing platform. Her PhD involved the study
of cancer and associated non-communicable diseases, with a focus on the three main areas of risk
including disease diagnosis, recurrence risk reduction and prevention of medication side
effects/therapeutic failure. She furthermore obtained a clinical MSc (Med) Genetic Counselling degree
(University of Cape Town) with published research on the return of individual genetic results and
incidental findings obtained with whole exome sequencing. She is passionate about reducing the South
African cancer burden through translatable research, fostering research innovation and improving
medical/genetic literacy and patient access to genetic services for ethical implementation of
personalised medicine.

Dr van der Merwe’s passion was realised in 2020 when she became the first healthcare practitioner in South Africa to perform genetic testing of BRCA1/2 and other non-communicable disease (NCD)-associated genes in breast cancer patients in the clinic during the genetic counselling, using new ParaDNA point-of-care technology developed by Gknowmix in collaboration with Stellenbosch University. During the same year while working with Prof Kotze as the Open Genome Project (OGP) Manager, the research team received a recognition for Best Practice in Precision Medicine by the International consortium for Personalised Medicine (ICPERMED) for the “Development of a pathology-supported genetic testing platform for point-of-care DNA testing using an integrated service and research approach” (https://www.icpermed.eu/en/798.php). Four years later after completion of the OGP, she is delivering two CPD-accredited talks on the ethical framework developed as part of the OGP for combining routine service delivery with genomics research. The recording of first talk (PART I) presented on 22 May 2024, is accessible here: Google Drive for 1 Ethics CPD point following completion of a google questionnaire.

The Open Genome Project that was initiated in November 2018 and completed in December 2023, aimed to gather various patient data to generate adaptable
patient genomic reports, presented as individual case studies. By integrating information from various fields including clinical, genetic, pathology-based,
environmental and lifestyle data, it furthermore aimed to deliver patient-centered care within a robust framework for personalized health interventions.
Collaborative knowledge-sharing improved processes from patient sample collection to result delivery and upheld ethical values, benefiting participants,
researchers, and funders. Three innovations developed under the pathology-supported genetic testing platform to foster diverse perspectives as part of the OGP
include a mobile application and wellness survey for risk assessment using the first level data processing algorithm; rapid point-of-care testing combined with
pathology data to guide patients to the right care pathway using the second level algorithm; and next-generation sequencing for detailed patient reports using the
third level algorithm.

A highlight of this oncogenomics meeting was a question posed by Dr Linda Jones, a local surgeon, about patients and their families who were previously
diagnosed with cancer but did not undergo genetic testing due to historical funding and follow-up issues. She emphasized the urgency of reinvestigating these
high-risk individuals. Mr Jaco Oosthuizen (medical scientist) acknowledged the challenges in following up with families in the public sector, citing a number of
limitations including the availability of resources and that of variant interpretation capabilities. The discussion also covered the importance of securing research
funding to support genetic counsellors who are trained to follow up patients and families. The potential use of pre-screen reports to engage patients by providing
personalized clinical profiles and raising awareness about the importance of genetic testing, was furthermore highlighted during these discussions. This tool can
help start the conversation with patients about their genetic risks and the benefits of further testing.

The conversation at the end of the talk furthermore emphasized the need for collaboration among healthcare providers, researchers and genetic counsellors to
follow a comprehensive approach to cancer prevention and patient follow-up. The meeting concluded with a plan to continue discussions and develop actionable
strategies, including application for new research funds and implementing point-of-care testing to increase access to genetic services. The participants expressed
interest in ongoing collaboration and support for initiatives that will enhance the follow-up process and improve patient outcomes, highlighting the need for a
structured program that overcomes the limitations of isolated projects. This led to the conceptualisation of an Open Genome Programme to be further planned
during the coming months. The meeting ended with an invitation to the next talk, PART II – taking place on 3 June 2024, for further multidisciplinary engagement
and continued communication and planning to achieve these goals.

Open Genome Project (OGP) Update: December 2021

We thank all the members of the Scientific and Technical Advisory Panel (STAP) and every co-author of the peer-reviewed articles listed below for your instrumental role and valued contributions to successful completion of the OGP. 

 

Our funders, the Technology Innovation Agency (TIA) of South Africa, approved extension of this project in the form of an implementation study with a strong focus on training. This will be done in line with the genomics framework published in February 2021 as several STAP members contributed to this Policy Paper:  

  • Accelerating Excellence in Science in Africa (AESA). A Framework for the Implementation of Genomic Medicine for Public Health in Africa [version 1; not peer reviewed]. AAS Open Res 2021, 4:9 (https://doi.org/10.21955/aasopenres.1115149.1)

 

During 2021 we hosted five virtual Oncogenomics Meetings to communicate international research results and some of our findings from studies performed in South Africa partly funded by TIA (2020-2021):

  • Mampunye M, van der Merwe NC, Grant KA, Peeters AV, Torrorey-Sawe R, French DJ, Moremi KE, Kidd M, van Eeden PC, Pienaar FM, Kotze MJ. Pioneering BRCA1/2 point-of-care testing for integration of germline and tumor genetics in breast cancer risk management: A vision for the future of translational pharmacogenomics. Front Oncol 29 September 2021. https://doi.org/10.3389/fonc.2021.619817. – PRESENTED BY DR RIKA PIENAAR
  • Myburgh EJ, de Jager JJ, Murray E, Grant KA, Kotze MJ, de Klerk H. The cost impact of unselective vs selective MammaPrint testing in early-stage breast cancer in Southern Africa. Breast 2021; 59: 87-93. ISSN 0960-9776, https://doi.org/10.1016/j.breast.2021.05.010. – PRESENTED BY DR ETTIENNE MYBURGH 
  • Oosthuizen J, Kotze MJ, Van Der Merwe N, Myburgh EJ, Bester P, van der Merwe NC. Globally Rare BRCA2 variants with founder haplotypes in the South African population: Implications for point-of-care testing based on a single-institution BRCA1/2 next-generation sequencing study. Front Oncol 2021; 10:619469. doi: 10.3389/fonc.2020.619469. PMCID: PMC7908826.
  • Baatjes KJ, Peeters AV, McCaul MH, Conradie MM, Apffelstaedt JP, Conradie M, Kotze MJ. CYP19A1 rs10046 pharmacogenetics in postmenopausal breast cancer patients treated with aromatase inhibitors: One-year follow-up. Curr Pharmaceutical Des 2020; 26(46):6007-6012.
  • Glanzmann B, Jooste T, Ghoor S, Gordon R, Mia R, Mao R, Charls P, Douman C, Kotze MJ, Peeters AV, Esser M, Tiemessen CT, Wilkinson RJ, Louw J, Gray G, Warren RM, Möller M, Kinnear C. Human whole genome sequencing in South Africa. Sci Rep 2021; 11: 606. doi: 10.1038/s41598-020-79794-x.PMID: 33436733; PMCID: PMC7803990.
  • Torrorey-Sawe R, van der Merwe N, Mining SK, Kotze MJ. Pioneering informed consent for return of research results to breast cancer patients facing barriers to implementation of genomic medicine: The Kenyan BRCA1/2 testing experience using whole exome sequencing. Front Genet 2020; 11(170):1-6. https://doi.org/10.3389/fgene.2020.00170.
  • Tod B, Schneider JW, Bowcock AM, Visser WI, Kotze MJ. The tumor genetics of acral melanoma – what should a dermatologist know? JAAD Int 2020; 1: 135-147

 

The importance of pharmacogenetics

Pharmacogenomics-based drug selection and dose adjustments help doctors to determine which medications are most likely to be effective or of no benefit to a patient due to impaired metabolic activity. The CYP2D6 enzyme function, for example, is of particular importance in selecting antidepressants causing moderate to severe side effects in 5-30% of people who take them due to their genetic make-up. Read More. In women treated with tamoxifen to reduce the risk of breast cancer development or recurrence, use of aromatase inhibitors is a reasonable alternative but the risk of osteoporosis may be increased in some patients. Read More.

How we use genetic research for disease prevention.

A pathology-supported genetic testing algorithm incorporating point-of-care BRCA1/2 testing is used to help determine the need for whole exome/genome sequencing in patients diagnosed or with a family history of cancer. Read More. In addition, genes and lifestyle/environmental factors involved in all the major NCD pathways are evaluated as previously described in relation to hypercholesterolaemia, homocysteine accumulation, blood clotting, iron overload/deficiency and drug metabolism. Read More.

Your genes load the gun, and your lifestyle pulls the trigger.

Every year millions of families worldwide are affected by lifestyle-related diseases with a genetic component such as cancer, depression, obesity, and heart disease – Read More…. This is mostly caused by over-consumption of alcohol, sugar, processed foods and inactivity. Physical and mental health are valued as the most important aspects of life, but even with technological advances it is difficult to make the right choices. Epigenetics is the effects seen on gene expression as a result of external factors that could positively or negatively influence health or disease progression – Read more.