Ethical Legal and Social Issues (ELSI) in Rare Conditions Research and Clinical Practice
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
Individuals and families living with rare conditions can benefit greatly from genomic technologies by, for example, providing a diagnosis (sooner) and having access to clinical trials and new treatments. The Ethical, Legal and Social Implications (ELSI) of genomics require attention because for example, the longevity, predictive, familial and uncertain information contained within these tests is not always obvious for mainstream specialties or patients requesting such tests. Our Node is the Rare ELSI Node and is a partnership between Manchester, Oxford and Cardiff. We are committed to addressing important issues such as; consent to testing and taking part in clinical trials; living with an undiagnosed rare condition; access to genomic testing through, for example, paediatrics or neurology; the psychological and social impact of rare conditions; and the design of clinical trials for treatment of rare conditions. We will work with patients, families, communities, clinicians, academics and industry to speed up research and drive innovation in issues ranging from referral pathways to the impact of rare conditions, and the design of clinical trials for treatments of rare conditions.
For the Manchester project (Impact and outcomes in rare condition clinical trials), we will first look at which outcomes are currently being used in rare condition clinical trials and how these are measured. Outcomes are things like measuring a patient-participant's symptoms and how patient-participants feel and function. Following this we will talk to patients and families to find out what their needs, hopes and expectations are, and what they consider to be meaningful improvement in the context of clinical trials. Then we will discuss what we have found with patient groups and others including experts in designing and assessing clinical trials, clinical geneticists, nurses, paediatricians, genetic counsellors and industry. This discussion will focus on what needs to be done to develop ways to measure the outcomes of rare condition clinical trials that are relevant for families and patients. The discussion will also lead to guidance to develop ways to measure outcomes that are valid and reliable.
For the Oxford project (Living with an undiagnosed rare condition) we will begin by analysing existing data from the Clinical Ethics, Law and Society research group (approximately 300 interviews) looking at people's first hand experience of living with an undiagnosed rare condition. From this we will identify points to explore initially through a workshop with those experiencing/involved in the care of those with rare conditions. We will then go on to examine issues that require further exploration through in-depth interviews with people and families with undiagnosed rare conditions to explore what it is like living without a diagnosis and how they feel they could be better supported.
For the Cardiff project (Barriers to mainstreaming) we will talk to practitioners and trainees in primary care and a variety of specialities in Wales and England about their experiences of genetic/genome-based investigations. Alongside this we will collect details about the referrals to clinical genetics services and to laboratories that are made to help with interpreting the results of genetic/ genomic tests or that suggest there may be a difficulty with how the results might be reported. We will arrange further contact with the practitioners and the patient groups to discuss how they would manage the de-identified difficult scenarios that we had previously 'collected'.
We will (1) develop and share suggestions to minimise the problems from handling genomics in mainstream specialties; (2) identify training needs of various specialties; (3) following discussions with patient representatives, Royal Colleges and UK specialty societies, we will develop proposals for good clinical practice and for the training of future specialists.
For the Manchester project (Impact and outcomes in rare condition clinical trials), we will first look at which outcomes are currently being used in rare condition clinical trials and how these are measured. Outcomes are things like measuring a patient-participant's symptoms and how patient-participants feel and function. Following this we will talk to patients and families to find out what their needs, hopes and expectations are, and what they consider to be meaningful improvement in the context of clinical trials. Then we will discuss what we have found with patient groups and others including experts in designing and assessing clinical trials, clinical geneticists, nurses, paediatricians, genetic counsellors and industry. This discussion will focus on what needs to be done to develop ways to measure the outcomes of rare condition clinical trials that are relevant for families and patients. The discussion will also lead to guidance to develop ways to measure outcomes that are valid and reliable.
For the Oxford project (Living with an undiagnosed rare condition) we will begin by analysing existing data from the Clinical Ethics, Law and Society research group (approximately 300 interviews) looking at people's first hand experience of living with an undiagnosed rare condition. From this we will identify points to explore initially through a workshop with those experiencing/involved in the care of those with rare conditions. We will then go on to examine issues that require further exploration through in-depth interviews with people and families with undiagnosed rare conditions to explore what it is like living without a diagnosis and how they feel they could be better supported.
For the Cardiff project (Barriers to mainstreaming) we will talk to practitioners and trainees in primary care and a variety of specialities in Wales and England about their experiences of genetic/genome-based investigations. Alongside this we will collect details about the referrals to clinical genetics services and to laboratories that are made to help with interpreting the results of genetic/ genomic tests or that suggest there may be a difficulty with how the results might be reported. We will arrange further contact with the practitioners and the patient groups to discuss how they would manage the de-identified difficult scenarios that we had previously 'collected'.
We will (1) develop and share suggestions to minimise the problems from handling genomics in mainstream specialties; (2) identify training needs of various specialties; (3) following discussions with patient representatives, Royal Colleges and UK specialty societies, we will develop proposals for good clinical practice and for the training of future specialists.
Technical Summary
Genomic technologies hold great promise to bring benefits for individuals and families living with rare conditions (RC) in terms of diagnosis and treatment. The Ethical Legal and Social Implications (ELSI) of genomics have received considerable attention, but their integration into RC research has lagged behind.
Objectives: (1) Improve the design of clinical trials for RC; (2) Understand the impact of living with undiagnosed RC; (3) Highlight barriers to mainstream access to genomic testing; (4) Develop proposals for good clinical practice.
O1: We will (1) undertake secondary data analysis to understand the outcomes and instruments used in RC clinical trials; (2) explore patients' views on meaningful improvement in the context of clinical trials; (3) integrate primary and secondary data and analyse with key stakeholders; highlight efforts needed to develop new instruments; (4) provide guidance to develop reliable instruments and core outcome sets for clinical trials.
O2: We will undertake secondary analysis of qualitative research data (from the 100k Genomes Project) looking at people's lived experience of undiagnosed RC; and hold a hybrid workshop with key stakeholders to discuss research findings. We will collect new empirical research from patients and families currently accessing the NHS GMS, and co-design means for better supporting patients and families.
O3: We will (1) work with practitioners in primary care and mainstream specialities in Wales and England; (2) note for one year referrals to GMS made to resolve difficulties with the interpretation of genomic tests results; and lab referrals from mainstream specialties that suggest difficulties with how the results might be reported; (3) contact practitioners and patient groups to discuss how they would manage difficult scenarios.
O4: We will (1) develop guidance to minimise challenges for mainstream specialties; (2) identify training needs; (3) develop proposals for good clinical practice.
Objectives: (1) Improve the design of clinical trials for RC; (2) Understand the impact of living with undiagnosed RC; (3) Highlight barriers to mainstream access to genomic testing; (4) Develop proposals for good clinical practice.
O1: We will (1) undertake secondary data analysis to understand the outcomes and instruments used in RC clinical trials; (2) explore patients' views on meaningful improvement in the context of clinical trials; (3) integrate primary and secondary data and analyse with key stakeholders; highlight efforts needed to develop new instruments; (4) provide guidance to develop reliable instruments and core outcome sets for clinical trials.
O2: We will undertake secondary analysis of qualitative research data (from the 100k Genomes Project) looking at people's lived experience of undiagnosed RC; and hold a hybrid workshop with key stakeholders to discuss research findings. We will collect new empirical research from patients and families currently accessing the NHS GMS, and co-design means for better supporting patients and families.
O3: We will (1) work with practitioners in primary care and mainstream specialities in Wales and England; (2) note for one year referrals to GMS made to resolve difficulties with the interpretation of genomic tests results; and lab referrals from mainstream specialties that suggest difficulties with how the results might be reported; (3) contact practitioners and patient groups to discuss how they would manage difficult scenarios.
O4: We will (1) develop guidance to minimise challenges for mainstream specialties; (2) identify training needs; (3) develop proposals for good clinical practice.
