Consumers Flashcards
What is 2 components of personalised medicine
Coupling established clinical-pathological indeces (signs/symptoms/imaging/biochemistry)
With
Molecular profiling
(profiling genes, cellular metabolism, protein signalling, disturbances in homeostasis)
How does POC testing help achieve personalised medicine
Diagnosis is quick and timely - no matter the setting to enable quicker point of care diagnosis
What is the generic standard care
Diagnostic triage - signs/symptoms/history
Treatment - generic guidance e.g. infectious diseases = broad spectrum antibiotic effective against gram negative bacteria
Patient monitoring,diagnostic confirmatory tests etc.
What is the INNOVA
Antigen test used to detect SARS-COV-2
What drives and enables the use of point of care testing to achieve personalised care
Drives
Clinical need
Utility - to change outcomes, reduced epidemiological burden
Enables
Technology - microfluidics and miniaturisation for rapid testing
Wireless communications
What are the requirements for a point of care test
Low cost or high return (cost effectiveness)
Rapid
Clear diagnostic threshold
Actionable
Simple
Match the gold standard
What are the 4 measurements of a good assay
If you give a group of just + or - how many people can they actually detect
Sensitivity (true positive rate)
Specificity (true negative rate)
Positive predictive value (PPV) - true positives divided by all positives found
Negative predictive value (NPV) - true negatives divided by all negatives
These are both linked to prevalence
As prevalence creases PPV decreases (more false positives) but NPV increases
What are some examples of point of care tests
Cholesterol finger prick
UTI’s and urinary dip stick
Lateral flow devices including COVID and pregnancy tests
What are nucleic acid amplification tests
PCR is one technique
The tests combine processing and testing in a single cartridge
Describe the use of the urinary dipstick
Urinary dip stick - performed In the home, primary and secondary care setting
Typically several tests are performed on one stick detecting multiple analytes
For example glucose, protein, blood, nitrite, and leukocyte esterase etc.
Commonly used to determine :
Bacteriuria – bacterial presence in the urine or
Pyruria – abnormal white cell presence in urine
Why does the urinary dipstick measure multiple things and why is this beneficial
Individually blood, nitrite, and leukocyte esterase have sensitivity from 23% up to 64% although the blood test on its own isn’t diagnostic of only bacterial infection
Any two of these combined then has a sensitivity of 74% providing greater diagnostic value
Determine between differential diagnoses
Describe lateral flow devices
Device used anywhere
Compatible with multiple analyte types e.g. antigens or antibodies
These analytes are carried through a membrane by a buffered solution via capillary action
These combine with labelled molecules and capture molecules (antibodies)
Concentration of the labels give rise to colour
Describe how the INNOVA device works
It is a lateral flow device where the sample is applied to the buffered solution which is wicked by capillary action
It flows over pads which capture and label the molecules e.g. by colloid gold
The reactants disolve so only labelled analyte is left, and additional molecules bind the control and test bringing a rise to colour in the test sample
What are the positives of INNOVA lateral flow testing
It’s cheap, easy to develop and mass produce
It’s simple and easy to use avoiding user errors
What are the disadvantages of INNOVA lateral flow testing
Lower sensitivity especially at lower viral loads typified by asymptomatic individuals
LFTs generally have limited applications because of the sensitivity and type analytes they can detect
What are the analytes of lateral flow tests
Antibodies, antigens and, uncommonly, nucleic acids
What mechanism is lateral flow nucleic acid tests based on
Complementarity of nucleic acid sequences
Hybridisation and detection of a captured duplex molecules
Hybridisation also allows for some amplification of the signal but not through amplification of the target molecule so sensitivity still does not match NAATs
What do HIV seroconversion lateral flow tests test for
Example = BioSURE
Tests for HIV antibody
What technologies facilitate advances in rapid point of care testing
Smart materials - nanomaterials, nanowires, paramagnetic beads
Miniaturisation -microfluidics and microelectronic machines (MEMs)
Microelectronic detection - electrochemical and fluorescent detectors
Disposable cartridges - facilitates modular assay design
Low power requirement
Smart devices/wireless
What does the GeneXpert do
This desk top system has off the shelf real-time PCR assays
Its capable of performing
Detection – presence or absence?
Quantification – measuring bacterial or viral load?
Variant detection –predicting antibiotic resistance?
What instruments are in the GeneXpert
The instrument comprises of simple microfluidic cartridge allows non-expert handling and containment
Modular system offers flexibility , extensibility
Each cartridge processes a different assay and sample
What are the benefits of GeneXpert
Sample processing integrated within the cartridge making it useable for non-expert operators
The small reaction volumes provide speed and While-U-Wait processing of less than 90min
The connectivity and user interface enables and easy to understand and actionable results
What is the bink IO system for STI’s
Similar to GeneXpert also based on microfluidic cartridges
It can perform 24 NAATs on a single sample - saves time and repeat sample collection
How does the binx IO system work in contrast to the GeneXpert system
• It uses microelectronic detection rather than traditional fluorescent detection like the cephid
Give some examples of direct to consumer testing companies
DNA testing - these include 23 and Me, AncestryDNA
What is genetic testing
Determining which variant, or variants, a person has
Giving advice on the basis of what the current state of knowledge is about those variants
Brings about ethical issues, and what it may mean to someone without a genetics BG
What are the different levels of detail of genetic testing
Single gene
Gene panel
WES
WGS
What can genetic tests be used for
Diagnose disease, and the factors that may have causes your disease as well as other risk factors
Predict how severe it may be, and the best medicine/dose
Find genetic factors that can be passed onto children, and screening of newborns
Briefly describe gene panels
Gene panel testing is carried out using NGS to screen for variants in 10s-100s of genes
WES may supersede gene panel testing as this is becoming cheaper
Commonly used in cancer
Briefly describe genome wide testing methods
Microarray based - SNP’s and CNV’s
Only looks for known mutations
NGS - WES and WGS
As NGS becomes cheaper it will become the preferred technique
What are some examples of single gene/variant tests
Haemoglobin for haemoglobinopathies
Many enzymes for metabolic disease
CFTR for cystic fibrosis
BRCA1/2 for breast and ovarian cancer
HTT for Huntington’s disease
What clinical features do some DTC companies test for
23 and Me screen for carrier status (heterozygote) of 42 rare diseases
Cystic fibrosis, phenylketonuria, sickle cell anaemia
Carrier because disease should be evident in people homozygous for disease-causing variants
Uses include family planning and informing future treatment e.g. in sickle cell anaemia for heterozygotes
What is the drawback to DTC cancer risk assessments
23 and Me test for only 3 of 1000s of BRCA mutations, which only appear in Ashkenazi Jewish populations
BRCA1 - 185delAG and 5382insC
BRCA2 - 6174delT
And they account for ~10% breast cancer and 15% of ovarian cancer
Describe ApoE testing
Alzheimer risk increases with ApoE 4
23 and Me users can opt out - ethical issues with being told life changing information without further support
List two uses of non clinical DTC test
Paternity and ancestry and other ‘fun genomics’ (eye colour, bitter taste, alcohol flush), health and fitness, animals
What are some of the terms and conditions of DTC
- Genetic info is permanent and has implications
- New info can arise in future
- You may learn things you do not anticipate which may have social, legal and economical implication
- Lab may not be able to process/there may be errors
- You shouldn’t change your behaviours solely on DTC info
- Genetic research is not comprehensive
Positives of DTC testing
- Patient choice/right/empowerment
- Not on record (insurance issues)
- Encourage planning for future/lifestyle changes/treatment
- Regularly updated and accessible info
Negatives of DTC testing
Incidental findings
Radical lifestyle changes may follow - take on or abandon healthy lifestyles
Distress for finding risk for a disease, without treatment
Your results may affects others in the family
Environment is very important in common disease risk variants
Literature changes all the time
Good company would ensure they would update the information, but not all do
Consumer protection
Hard to apply the law, so are consumers protecting enough
Clinical concerns of DTC
Dr Google - clinicians having to sort out patient distress
Lack of genetic counselling
Patient ability to understand results - do they have the right level of education
Increases patient anxiety
Questionable clinical utility - is it actionable
If the doctor cannot help, this impacts the patient relationship
Not being able to answer patient questions
Taking information from various sources with questionable reliability
DTC may be advertising/bias for drug companies
Consumer protection
Protection from ourselves, society, commercial interests - e.g. insurance, employers, and the nation state
What defines an individual
Personal data – information identifying a person
Personal sensitive data – information about an individual including health records
What are the UK acts for data protection
UK = 1998 Data Protection Act, 2018 General Data Protection Act
What are examples of information defining an individual in a health context
Their characteristics – age gender, social and behavioural metrics
These are biochemical, physiological and genetic
The results of tests that describes them
Their health and wellbeing past present and future
How does GDPR define genetic data
“Personal data relating to the inherited or acquired genetic characteristics of a natural person which give unique information about the physiology or the health of that natural person and which result, in particular, from an analysis of a biological sample from the natural person in question”
How does GDPR define health data
“Data concerning health” means personal data related to the physical or mental health of a natural person, including the provision of health care services, which reveal information about his/her health status
Why is GDPR for health and genetic data important
To meet UN declaration of human rights - to be equal, without discrimination and have a standard of living for health and well-being and the right to access medical care and social services
What do we need protection from in regards to DTC genetic testing
Quality, validity and utility, regulation
Legality and social norms - eugenics?
Psychological and physical harm - any follow up?
Discrimination - work, society, healthcare, insurance
What types of discrimination may someone face
Chambers dictionary - unfair treatment of a person, racial group, minority, etc; based on prejudice
Insurers - rational vs irrational discrimination – rational personal predictive risk assessment based on risk an individual brings to the pool
Lawyers - legal vs illegal discrimination
Patients - differential/negation of treatment based on current, past health or their future health risk
What is the stance on genetic infromation
It is wildly different and conflicting
These views are often influenced by socioeconomic deprivation, lack of national resources, immigration and globalisation
This conflict can lead to shifts in acceptability e.g. reproductive freedom
Is there systematic evidence of genetic discrimination by insurers
Evidence is poor/limited/out of proportion to the intensity of debate and legislative attitudes
What factors should be consider in regards to protections regarding genetic tests
Regulation of (genetic) test devices and tests also driven in part by biomedical ethics
Human Rights and Privacy - ownership of health information, concept of “genetic exceptionalism”
Who drives regulation
Regulation is driven by biomedical ethics or bioethics
The accepted norms of societal behaviour
Universal Declaration on Bioethics and Human Rights (2005)
What is the minimum legislative framework
In Vitro Diagnostic Device Directive (IVDD 1998)
What does the In Vitro Diagnostic Device Directive (IVDD 1998) regulate
Regulates test methods and equipment
Not whether conclusions or medical advice drawn from the results benefit the consumer
Applies to commercial genetic tests for health purposes only
What are the exemptions within the IVDD
Exemptions:
“in house” or Laboratory Diagnostic Tests (LDTs)
Enables flexibility for introducing and developing tests in local healthcare systems
“non-health related” and direct to consumer tests e.g. 23 and Me
What is the UK volunatry regulatory agreements
• Clinical Pathology Accreditation UK Ltd scheme and other voluntary schemes (that NHS REQUIRE)
and
UK Genetic testing network
What does the Clinical Pathology Accreditation UK Ltd scheme do
Ensures regular inspection and quality of laboratory service
Does not apply to the clinical efficacy or interpretation of the results
What does the UK genetic testing network do
Advisory organisation that provides commissioning support to the NHS and DH on behalf of NHS patients in the UK
Promotes quality and equality of access across the NHS
What are the bioethics regulations
• Council of Europe Convention on Human Rights and Biomedicine (1997,2008)
What does the Council of Europe Convention on Human Rights and Biomedicine (1997,2008) regulate
Legally binding to signatories, requiring parliamentary ratification and passing into national law
Applies to tests for ‘health purposes’ includes specifically genetic tests and services
Does not apply to DTC as it is ‘not for health’
Requires that these are of appropriate quality, validity and utility
Not ratified in UK, ROI, Germany etc.
Who are the consumers most concerned about when it comes to their privacy
The privacy from employers, insurers, and the government - less so from commercial entities
What are international regulations for privacy in health infromation
Rights defined by UN Human Rights Act 1948 and subsequent Acts, Conventions and Treaties
Treaty of Functioning of the EU 1958
EU Charter of Fundamental Rights 2010/12
European Convention on Human Rights 1953 and Biomedicine was added 1997, 2008 (articles 7 and 12) – specifically refers to genetic testing
European legislation is a framework with national exemptions and extensions
Council of Europe Recommendations of 1997
Health and genetic data handling, it defines autonomy, incidental findings and privacy
What is the bioethic regulation on genetic data
International Declaration on the Human Genome and Human Rights (1997)
Declaration on Human Genetic Data (2003) Article 4
These specifically cites genetic data - no one should be subject to genetic discrimination because it may be predictive, have impact and significance at all levels of society
What legislations define ownership of health information and data protection
Data Protection Directive (DPD 1995) concerns protection of individuals, privacy and the movement of personal information
Refers to health-related information
Allows for limited derogation (lowering) of the rules on privacy applies for societal protection, health insurance, governmental functions etc
General Data Protection Regulation (GDPR 2016)
Specifically include genetic data and advances in technology in a new directive
What legislations may insurance companies be bound to
Voluntary Concordat (2005) and Moratorium (2001-2018, rolling code of practice from 2018)
Association of British Insurers (ABI) has operated a moratorium on asking for and using results for predictive genetic tests of an individual or relative
Applies to any test diagnostic or predictive test, including DTC genetic tests, WGS as part of 100K Genomes Project
What are the limitations of the legislations insurance companies are bound to
Does not apply to non-genetic predictive tests i.e. someone who is asymptomatic or where a test provides predictive benefit excluding a condition for an individual
Nor diagnostic tests
If the genetic condition is diagnosed, it is not protected
Exemptions and conditions apply e.g. specific tests Huntington’s Disease or above a specific insurance of value
